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ISSN : 0915-1478 CODEN : FFRDEK 60, 1-195 (2015) No.60—2015 PURPOSE OF PUBLICATION This annual publication is issued in order to introduce the results of research and development carried out in the laboratories of FUJIFILM Corporation and its subsidiaries. To provide an overview of our wide-ranging R&D activities across numerous business ﬁelds, this collection inc1udes the papers, which are new1y written or have already been published in various science and technology journals, regarding our noteworthy new products and novel technologies. In addition, a list of such papers published in journals and those presented at academic conferences in the past one year is attached at the end. © FUJIFILM Corporation 2015 Published by Strategic Corporate Technology Planning Division, Research & Development Management Headquarters, FUJIFILM Corporation Nakanuma, Minamiashigara, Kanagawa, 250-0193, Japan Kouichi Tamai Foreword Director and Executive Vice President FUJIFILM Corporation I served as Division Manager of FUJIFILM s Medical Systems Business Division and Director of the Medical System Research & Development Center. In my role as Director of the R&D Center, I envisioned and developed products, which was an unusual job assignment. The double workload increased response speed and R&D productivity. In other words, I was obliged to quicken my pace. The current problems in our R&D activities are low yields of newly developed products and slow development speed. Some R&D personnel may disagree with this assessment for the following reasons: (i) they have conﬁdence in their achievements and are unwilling to accept such a low opinion; (ii) they believe that yields of new products are naturally low; and (iii) they are indifferent or believe that developing new products is always difﬁcult. Granted, launching new products is not easy. However, maintaining motivation to develop new successful products and ensure speedy development is essential. I am also concerned about how deeply researchers are involved in the marketing of new products. Researchers should not focus only on products speciﬁed by the business division. A common issue that applies to R&D members and FUJIFILM employees, in general, is that they try to postpone cost and pricing considerations. Some think that a priori discussions about money are harmful and believe that they scare clients and partner companies. However, this is deﬁnitely wrong. Forthright consideration of ﬁnancial matters is an indication of reliability. I have also seen many cases in which initial cost planning and price setting are too optimistic. Costs and selling price must be evaluated throughout the development process. We have allowed overly optimistic attitudes to become entrenched. Only FUJIFILM can create this product. Comparable products from other companies cannot achieve the same level of performance as ours. A good product should sell at a high price. FUJIFILM has excellent human resources. However, so do our competitors. Then, how can we defeat them? In his book about restructuring Japan Airlines, Chairman Emeritus of Kyocera, Kazuo Inamori, said that that exerting more effort than your competitors is key. I agree. I studied mechanical engineering, and throughout my long career, I have developed many pieces of industrial equipment. Of course, I have experienced failure, but overall, the yield has been relatively high primarily because I always examined technology against cost competitiveness and asked whether the selected mechanism was appropriate and could achieve its purpose at minimum cost. Although I am now a manager, I intend to continue my studies in mechanical engineering. Without continuous advancement of knowledge, an executive s mind becomes too narrowly focused. Even now, at R&D meetings, I often illustrate equipment on the whiteboard. 3D illustrations will help us realize the form of ﬁnished products and share issues. Can our R&D executives still make a contribution standing in front of a whiteboard? Or do they merely complain and leave the conceptualization of new products to younger personnel? New product creation is essential to put FUJIFILM back on track and to consolidate its growth. We need to outperform our competitors, even if only by a narrow margin. To do so, it is important to launch products into the market as quickly as possible. Executives and R&D personnel are equally responsible for developing products that outperform our competitors. FUJIFILM RESEARCH & DEVELOPMENT No.60 CONTENTS Originals Development of Jet Press 720S Digital Inkjet Press ....................................................... Tsutomu KUSAKARI and Tsuyoshi MITA ...... 1 Development of Next-generation Ultra-lightweight Cassette DR CALNEO Smart .................................................. Makoto KITADA， .................................................... Akihito BETTOUYASHIKI，Sho SHIMIZUKAWA，Takashi TAJIMA，and Ryosuke OGURA ...... 6 Development of a Next-generation CCD Imager for Life Sciences Research ........................ Seishi IKAMI，Takashi KOBAYASHI， ....................................................................................................................................... Yasutake TANAKA，and Akira YAMAGUCHI ...... 10 Improvement in Image Quality and Workﬂow of X-Ray Examinations using a New Image Processing Method, Virtual Grid Technology ..................................................... Takahiro KAWAMURA，Satoshi NAITO，Kayo OKANO，and Masahiko YAMADA ...... 21 Quantiﬁcation of the Respiratory Activity of the Lung using CT Images ........................ Takayuki HASHIMOTO，Caihua WANG， .................................................................................................................................................................................. and Jun MASUMOTO ...... 28 Development of Quantitative Immunoassay Reagent FUJI DRI-CHEM IMMUNO AU Cartridge vc-TSH and v-COR ................................................. Hiroyuki CHIKU，Junichi KATADA，Tomoya OHARA，Noriyuki KASAGI，Atsuhiko WADA， .......................................................................................................................................................................... and Kentaro NAKAMURA ...... 33 Development of a Hair Care Product Series, ASTALIFT SCALP FOCUS .................. Tomoko TASHIRO，Taichi MURAGUCHI， ......................................... Mayuko KANEHISA，Mikinaga MORI，Hiroyuki KITAOKA，Tomoko THIELE，Akihiro SUGITA， .................................................................................................................. Atsushi ORIKASA，Takuji KOSUGI，and Kozo NAGATA ...... 40 Development of Base Makeup Series ASTALIFT Lighting Perfection ......................................... Miki KINAI，Tomomi TATEISHI， ........................................... Kazuhiro NAKAMURA，Terukazu YANAGI，Ikuko OGARU，Noriko OHIRA，Naoko YOSHIDA， ........................................................................................................... Soichiro NAKAMURA，Eriko IKEDA，and Yasuko TAKEDA ...... 45 High Functionality of UV Inkjet Inks Produced by Combining an N-vinyl Compound ............................. Tsutomu UMEBAYASHI， ................................................... Toshiyuki MAKUTA，Mamoru TANABE，Tadao SHIBAMOTO，and Takahiro HAMAMOTO ...... 51 Development of a Long-life Processing System for Newspaper CTP Plates（LL-6） ................................................................................................................................ Toshihiro WATANEBE* and Tomoki OCHIMIZU* ...... 55 * Co-researcher outside FUJIFILM Corporation Development of “Jet Press 720S” Digital Inkjet Press Tsutomu KUSAKARI* and Tsuyoshi MITA* Abstract FUJIFILM released a new sheet-fed inkjet printer in 2014̶Jet Press 720S. Based on the previous Jet Press 720 model revealed in 2008, the Jet Press 720S has been developed with improved functions. We adopted the PZT sputtering process in the printhead for good uniformity among jets, new printhead maintenance technology for nozzles with fewer defects, and a simpliﬁed replacement process for defective printhead modules. These technological advancements have resulted in improved printing productivity. In addition, full-size variable printing was introduced to diversify the available printing services. 1. Introduction At Drupa 2008, FUJIFILM exhibited the technology of the Jet Press 720, a high-speed, high-resolution sheet-fed inkjet printer that enabled small-lot commercial printing. Later, the printer was launched onto the market.1) The company then developed the successor model, Jet Press 720S, and started its mass production in 2014, having established a good reputation with it. This paper describes the functions incorporated into the Jet Press 720S improving on its predecessor by achieving stable printing quality, increase in productivity via downtime reduction, and full variable-data printing. 2. Outline of the Jet Press 720S 2.1 Outline of the system The Jet Press 720S incorporates the following technologies that are inherited from and improve upon its predecessor, Jet Press 720. i. ii. iii. iv. v. vi. vii. High-density droplet jetting enabled by the highdurability MEMS printhead Printhead maintenance function to sustain highresolution printing High-speed cohesion technology to achieve high color reproducibility Water-based ink drying High-precision scanning with an inline scanner Image processing technology Full variable-data printing (optional) With those technologies, the printer has acquired a versatility that conventional offset printers lack and is now highly re- garded as an innovative printer that meets a variety of needs such as small-lot printing and quick delivery. The following are the system speciﬁcations of the Jet Press 720S. The appearance is shown in Fig. 1. Resolution: 　　　　　 1,200 dpi × 1,200 dpi Colors: CMYK (four-color) water-based pigment ink Paper supply method: Sheet-fed Maximum paper size: B2 (750 × 532 mm) Paper thickness: 　　　　　 0.105 to 0.34 mm Maximum printing speed: 2,700 sheets/hour Equipment dimensions: 8,019 mmW × 2,653 mmD × 2,050 mmH Weight: 　　　　　 14 t 2.2 Outline of the high-precision MEMS printhead To ensure high-precision color registration, the Jet Press 720S deploys a four-color compact piezo-based printhead with a resolution of 1,200 dpi and a width of 720 mm in one printing cylinder (Fig. 2). That realizes printing productivity of a maximum of 2,700 sheets per hour in single-pass printing. Fig. 1 View of Jet Press 720S Original paper (Received January 28, 2015) * Advanced Marking Research Laboratories Research & Development Management Headquarters FUJIFILM Corporation Takematsu, Minamiashigara, Kanagawa 250-0111, Japan FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 1 The printhead employs 1,200-dpi head modules consisting of 2,048 nozzles. By forming print bars, each consisting of 17 modules aligned with a high precision of a few micrometers, it achieves a wide printing width. The printhead is built with submicron-level, high precision and density via the microelectromechanical systems (MEMS) process, using silicon for the part from the ink channel to the nozzles. It is capable of jetting ink with a minimum droplet volume of 2.0 pL at 100 kHz and draws images by combining three different sizes of droplets, small, medium and large. Figs. 2 and 3 show the appearance of the printhead module manufactured by FUJIFILM Dimatix, Inc. and that of a print bar implemented with high precision, respectively. 3. Technologies incorporated into the Jet Press 720S The technologies to be incorporated into the Jet Press 720S were reviewed system-wide before implementation. Thus, new technologies, not only inherited from but also improvements on those of the Jet Press 720, were introduced into the printer. The following are the details of those technologies. surface with divided dummy jetting; (4) prevention of nozzle degradation caused by drying; and (5) addition of the printhead module replacement function. 3.1.1 Sputter-deposited ﬁlm for the piezoelectric actuator A sputtered ﬁlm with a high piezoelectric constant developed by FUJIFILM is used for the piezoelectric actuator of the Jet Press 720S (Fig. 4). Conventionally, a method has been used in which bulk PZT (lead zirconate titanate) is thinned via polishing. However, with our sputtering technology, it has become possible to streamline production processes, including polishing, and stabilize the ejection performance inside the module. In addition, sputtered PZT ﬁlms do not use adhesives and are highly heat-resistant, which improves ﬂexibility in high-temperature processes after ﬁlm deposition and enables the stable formation of protective ﬁlms with low moisture permeability on the surface. That prevents moisture penetration from affecting the life of the product. A rigorous endurance test, in which high-voltage pulses were applied 700 billion times experimentally in a high-humidity environment, achieved the excellent result that none of the 2,048 actuators failed at all and the displacement remained within 3%. The ﬁlm thus contributes to increased durability of the actuators (Fig. 5). Fig. 2 Inkjet print engine and printhead module Fig. 4 SEM micrograph of sputtered PZT Fig. 3 Print bar 3.1 Printhead-related technology By improving printhead durability and preventing deterioration in printing performance, it has become possible to reduce non-printing time and thereby increase actual productivity in printing.2) Speciﬁcally, the following improvements were made: (1) increase in the number of sustainable printing operations by making the piezoelectric actuator into a thin ﬁlm via sputtering; (2) nozzle surface wiping with a web (cleaning cloth); (3) prevention of ink adhesion to the nozzle 2 Fig. 5 Average displacement over time. Less time degradation of displacement occurs with recurring jetting pulses. Data points indicate when each jetting pulse occurred. Development of Jet Press 720S Digital Inkjet Press 3.1.2 Nozzle surface wiping with a web Long-term stable jetting of water-based pigment ink containing latex is difﬁcult to achieve. To ensure high jetting precision, high water repellency must be maintained in the vicinity of the nozzles. To that end, the printhead module is constructed with a high-durability, water-repellent ﬂuorocarbon ﬁlm on the nozzle surface and a structure that prevents the increase of ink viscosity near the nozzles by circulating ink inside the module (Fig. 6). In addition, to ensure stable jetting of the printhead, a maintenance function is newly introduced in which a web wet with a nozzle cleaning solution wipes off water-based pigment ink containing latex that easily dries and adheres to the nozzle surface (Fig. 7). That mechanism keeps the nozzle surface always clean and maintains high jetting performance of the printhead. Fig. 6 Schematic of ink circulation in printhead module (Fig. 8). That keeps the wiping count and damage to the nozzle surface by wiping friction to a minimum, thus enabling the reduction of non-printing time. Fig. 8 With and without divided dummy jetting 3.1.4 Technology to prevent nozzle degradation caused by drying To achieve high-speed ink cohesion and ﬁxation to paper, the Jet Press series printers use water-based pigment ink containing latex, which is resistant to adhesion to the nozzle and re-dissolution after solidiﬁcation compared with general water-based inkjet ink. The printers also employ a technology to prevent ink adhesion to the nozzle surface by optimizing the ink circulation pressure and nozzle surface pressure. Via the experimental optimization of individual pressures, it has become clear that the printers can prevent deterioration in jetting, due to adhesion caused by drying, by keeping a high ink circulation pressure and a high-precision, positive nozzle surface pressure. Reference values for typical pressures are given in Fig. 9. Under the conditions determined with this method, the drying deterioration rate slows six times compared with that under the standard initial conditions. Fig. 7 Outline view of web wiping system 3.1.3 Divided dummy jetting Before web wiping to ensure long-term stable jetting of water-based pigment ink containing latex, dummy jetting is carried out to eject ink that has its viscosity increased near the nozzles during print jobs. In addition to ink mist during print jobs, ink mist during the dummy jetting also adheres to the nozzle surface. Previously, it was therefore necessary to apply web wiping repeatedly to keep the nozzle surface clean. However, the Jet Press 720S performs dummy jetting, dividing it into several operations with multiple dummy jetting nozzles, and thereby considerably decreases the amount of ink mist generated by crosstalk between nozzles and keeps the adhesion of ink mist to the nozzle surface to a minimum 3.1.5 Printhead module replacement technology With the above described technologies, sustainability in the printing performance of the printhead module has further improved from that of the Jet Press 720. However, easy maintenance of degraded printhead modules is also desirable. The Jet Press 720S has achieved signiﬁcant improvement in maintenance performance and downtime reduction by introducing a module-by-module printhead replacement mechanism. FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 3 Fig. 9 Ink pressure control in printhead module The Jet Press 720S allows users to replace printhead modules, to adjust the position of the replaced modules in the order of micrometers and to correct their properties in the course of its operation. Quick response to deterioration in printing performance has thus become possible. Fig. 10 illustrates the outline of printhead module replacement. 3.2 High-speed ink cohesion technology Among continuously incorporated basic technologies are preconditioning of paper and high-speed ink cohesion. General inkjet printers are subject to bleeding of images with non-inkjet printer paper, such as that for offset printers, due to the expansion of dots. To realize high-quality, bleedingfree offset printing, the Jet Press 720/720S applies precon- Fig. 10 Replaceable printhead module ditioning solution to the paper before printing and thereby prevents bleeding. In that process, instantaneous ink cohesion takes place on the paper upon the reaction of the preconditioning solution with the ink, which maintains individual dot form without merging the neighboring dots (Fig. 11). As a result, a signiﬁcant inkjet printing issue, bleeding, is solved and reduction in text reproducibility is prevented (Fig. 12). High-speed ink cohesion has been realized by the development of our own pigment dispersant and latex. That same high-speed ink cohesion technology can also improve ink dot printing density, which may lead to the realization of widerrange color reproduction. The technology is thus one of our core inkjet printing technologies (Fig. 13). 3.3 Advanced image correction technology The Jet Press 720S incorporates an inline scanner that allows instantaneous scanning of printed images and dedicated correction-purpose charts inside the equipment. Scanning just printed images directly after the printhead of the printing cylinder enables the prompt detection of changes in the printing condition and the correction of images. That keeps the number of lost printing sheets to the minimum if the drawing condition changes during printing. With the image correction technology used in the Jet Press series, it is possible to correct white noise and irregular colors even when print nozzle jetting fails or is unstable. Without correction, any nozzles that do not eject ink produce white noise. In such cases, adjusting the intensity of drawing colors of the nozzles nearby can reduce the visibility of the noise (Fig. 14). Any large deviations detected in the ink jetting direction can also be corrected by disabling the relevant nozzles. Fig. 11 Ink-dot shapes with and without the preconditioning process Fig. 12 Letters printed with and without the preconditioning process Fig. 13 Color gamut of Jet Press series and Japan color 4 Fig. 14 Correction method for missing nozzle Development of “Jet Press 720S” Digital Inkjet Press Fig. 15 Image data ﬂow for variable printing Fig. 16 Image data ﬂow for reverse side variable printing 3.4 Variable-data printing The Jet Press 720S has newly incorporated, as an option, the variable-data printing function, particular to digital printers, that can be set for each print image in a continuous print job. During variable-data printing, four-color, full-speed printing is still possible (Fig. 15). In addition, in duplex printing, the Jet Press 720S performs real-time selection of images to be printed on the back print surface by printing a bar code on the front print surface of each sheet and later scanning the bar code with a dedicated reader at the feeder (Fig. 16). Speciﬁcally, if image types A, B, C, D, E are printed in sequence on the front print surface but the sheet order is accidentally changed to A, B, D, C, E before the back surface is printed, the Jet Press 720S will detect it by scanning the bar codes and can still print the correct images on the back print surface of the corresponding sheets. In that way, the printer enables automatic correction of human errors and missing sheets during duplex variable-data printing. Those functions are major advantages of digital printers that can be of signiﬁcant appeal, meeting a variety of needs in printing. References 1) Nakazawa, Y.; Yanagi, T.; Nagashima, K.; Inoue, Y. Development of Digital Inkjet Press Jet Press 720. FUJIFILM Research & Development. 2012, no. 57, p. 27-32. 2) Mita, T.; Nakazawa, Y.; Hishinuma, Y.; Shinada, H. Head Technology and Head Maintenance Technology for SheetFed Inkjet Printer (Jet Press 720) - Effect of Heat Treatment of Carrier Beads. Imaging Conference JAPAN 2014 Fall Meeting. Kyoto, Nov. 21, 2014. The Imaging Society of Japan. 2014. Trademarks ・ Jet Press referred to in this paper is a registered trademark of FUJIFILM Corporation. ・Any other company names or system and product names referred to in this paper are generally their own trade names or registered trademarks of respective companies. 4. Conclusion The Jet Press 720S is an advanced version of the Jet Press series that has undergone innovative improvements on the basic technologies inherited from the preceding models. To create new areas for more diversiﬁed printing business in the future and thus vitalize the industry, we are going to continue to develop technologies that will widen the range of printing media, increase printing speeds and further improve print quality. FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 5 Development of Next-generation Ultra-lightweight Cassette DR “CALNEO Smart” Makoto KITADA*，Akihito BETTOUYASHIKI*，Sho SHIMIZUKAWA*，Takashi TAJIMA*， and Ryosuke OGURA** Abstract In this paper, we report a newly developed cassette type DR called the FUJIFILM DR CALNEO Smart . CALNEO Smart is the world s lightest DR with a weight of 2.6 kg, and its innovative shape and high-quality internal circuit allow for dramatically improved workﬂow and low-dose diagnosis. A detailed explanation about CALNEO Smart is provided in this paper. In recent years, digitalization in the medical ﬁeld has been advancing rapidly and the use of digital radiography (DR) has been promoted in the X-ray imaging domain. Under such circumstances, FUJIFILM has increased the sales of the DR cassette CALNEO C with its high image quality that overwhelms the similar products of other companies. However, digitalization has also encouraged many electronics manufacturers and newcomers inside and outside Japan to enter the medical equipment industry, which initiated ﬁerce sales competition in that domain. We therefore developed the FUJIFILM DR CALNEO Smart (hereinafter, the CALNEO Smart ) that can improve imaging workﬂows dramatically, placing top priority on the requests of medical staff gained via our accumulated experience in that ﬁeld. This paper describes its various functions. Enhanced operability with innovative rounded-shape, protrusion-free design While being compliant to the ISO standard for cassette sizes, the CALNEO Smart has a prominent characteristic in appearance: the smoothly chamfered back side. That rounded shape helps to greatly reduce the physical load applied to users; for example, the pain that patients feel when the cassette is inserted under the body and the fatigue of technicians due to the resistance that they feel when inserting it (Fig. 1). In addition, the fully-ﬂat design, reducing as many protrusions and depressions (e.g., battery mounts, screws and labels) as possible, has realized high cleanliness and cleanability. The uniformity in design including even peripheral devices also contributed to the CALNEO Smart winning the Good Design Award for 2014, representing its innovativeness and exhibiting high presence (Fig. 2). 2. New functions that improve workflows dramatically 2.2 2.1 1. Introduction The CALNEO Smart has a variety of new functions in addition to the improved basic imaging functions necessary as a DR cassette. It can realize excellent usability regardless of the location, environment and domain. It is suitable for use not only in X-ray rooms of radiology departments but also in various other situations, such as walking rounds, home care and disaster relief operation. Compatibility of robustness, water resistance and the world’s lightest body The CALNEO Smart has employed a shellﬁsh structure for its housing (Fig. 3). The material used is light, high-strength magnesium and, by integrating stiffening ribs into the structure during die casting, the strength of the housing has been Fig. 1 Improvement in insertability of cassette because of the round shape Fig. 2 Innovative and uniform design including peripheral equipment Original paper (Received December 25, 2014) ** Design Center * Medical System Research & Development Center FUJIFILM Corporation Research & Development Management Headquarters Nishiazabu, Minato-ku, Tokyo FUJIFILM Corporation 106-8620, Japan Miyanodai, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8538, Japan 6 Development of Next-generation Ultra-lightweight Cassette DR “CALNEO Smart” increased even further. In addition, by redesigning the weak points discovered via dynamic analysis with the high-precision ﬁnite element method (Fig. 4), the world s lightest body of 2.6 kg with improved robustness has been realized. In particular, the extent of deformation to bending loads has been signiﬁcantly reduced, becoming approximately one sixth compared with that of the previous models. The CALNEO Smart is thus useful for portable imaging in unstable positions, such as on a stretcher in an emergency (Fig. 5). Moreover, the joints of the housing are sealed up, which achieves improved robustness as well as water resistance equivalent to IPX6 (a level at which there is no adverse effect caused by strong water jets from all directions) even when the body is loaded. That allows its use outdoors at disaster sites, etc., and cleaning with running water after use (Fig. 6). the photo ﬁlm domain in combination with a newly developed technology, HYDRO AG, utilizing the expertise in bacteria of Toyama Chemical Co., Ltd. In general silver-based antibacterial coatings, the binders in which antibacterial agents are dispersed lack hydrophilic properties. Therefore, without reaching the inner levels of the coating ﬁlm, moisture only reacts to the antibacterial agent exposed on the surface and elutes silver ions there. In contrast, the HYDRO AG uses a hyper-hydrophilic binder, which causes moisture to react to the antibacterial agent not only at the surface but also inside the coating ﬁlm. Silver ions are thus released gradually from inside and the surface silver ion concentration is kept high. In that way, the CALNEO Smart has acquired both high and lasting antibacterial performance that has never been achieved before (Fig. 7). In a JIS Z 2801-compliant test, one hour after 2.3 Antibacterial property bestowed by FUJIFILM’s own antibacterial coating HYDRO AG For the ﬁrst time as a DR cassette, the CALNEO Smart has introduced an antibacterial function into its housing surface. The antibacterial coating used is based on the silver and precision coating technology that FUJIFILM has cultivated in Fig. 5 Comparison between flexural deformation of CALNEO Smart and that of the previous model Fig. 3 Shellﬁsh shape of magnesium alloy Fig. 6 Waterproof test under load pressure (100 kgf) Fig. 4 Simulation of drop destruction by the ﬁnite element method FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) Fig. 7 Antibacterial mechanism of HYDRO AG 7 Fig. 8 Antibacterial performance of HYDRO AG contact with bacterial solution, the number of residual bacteria decreased below the detection threshold. In another test simulating a hospital environment, the CALNEO Smart was sprayed with bacterial solution and stored at 25°C and 50% RH. Six hours after the contamination, the number of residual bacteria decreased by 99.9% or more. In both tests, the coating function achieved a performance one hundred times better than that of the conventional technology (Fig. 8). into multiple regions to observe the ﬂow of barium. However, by considerably reducing the dark noise that occurs during long-term signal accumulation with a newly developed lownoise circuit, the CALNEO Smart has succeeded in lengthening the maximum signal accumulation period to 10 seconds, 2.5 times longer than that of conventional ones. It has thus become possible to replace X-ray ﬂuoroscopic equipment dependent on computed radiography with DR cassettes (Fig. 9). 2.4 Implementation of long-term accumulation mode The maximum signal accumulation period of conventional DR cassettes is approximately four seconds. That prevents them from being used in examinations that require long-term accumulation of signals, such as esophagography in which Xray exposure is performed several times for one image divided 3. Improvement of basic performance Fig. 9 Esophagram image of CALNEO Smart 8 In addition to the above described advanced functions, the CALNEO Smart has established further user-friendliness in usual imaging as well, by overall reviewing and improving basic DR technologies. 3.1 Realization of low-dose imaging DR cassettes generate images by outputting data digitally converted via the following processes: conversion of radiated X-ray signals into light with a CsI or GOS scintillator; conversion of the light into analog electrical signals using photodiodes; and reading the converted signals using TFTs. The detector of the CALNEO Smart has inherited the conﬁguration of the high-performance X-ray detection system with FUJIFILM s own ISS method (Fig. 10) that was already used in its previous models. By using a newly developed lownoise electrical circuit in combination with advanced image processing technology in the ﬁeld of FUJIFILM s expertise, the CALNEO Smart has achieved high image quality with half the conventional X-ray dose, while also obtaining a substantial improvement in the granularity of images. Development of Next-generation Ultra-lightweight Cassette DR “CALNEO Smart” Fig. 10 In the ISS method, converted light reaching the TFT surface is strong and sharp compared with the conventional side sampling (CSS) method; therefore, image quality is signiﬁcantly improved 3.2 Improvement in battery lifetime and recharge time In the CALNEO Smart, we have realized a reduction in the required battery capacity by maximizing the performance of each voltage conversion circuit based on a thorough review of the electrical circuits. That contributes to weight reduction. We also reviewed the behavior of the sleep mode that was already incorporated into the previous models, via which we have succeeded in seamless switching between the sleep mode and normal mode and in increasing the battery lifetime to approximately eight hours. In addition, to further extend the lifetime, we have employed a low power-consumption microcomputer chip and reduced power consumption by controlling voltage supply to the A/D convertor and image processing chip during idling. Consequently, we have realized a new extra sleep mode that achieves a battery lifetime of 18.5 hours. Normal mode, sleep mode and extra sleep mode can be selected arbitrarily depending on the situation (Fig. 11). With regards to battery recharge, the CALNEO Smart supports a new rapid battery recharging function for its main body, which shortens the recharge time from about 10 hours with the previous models to 4.5 hours. In addition, it provides a quick charge function to allow a small amount of imaging when the battery has gone ﬂat. With that function, a threeminute recharge enables the processing of approximately 30 images. In that way, the downtime when the battery unexpectedly gives out can be minimized. Fig. 11 Battery life improvement of CALNEO Smart compared with previous model 4. Conclusion As described, the CALNEO Smart is a next-generation DR cassette with a variety of new functions as well as basic performance further enhanced from the previous models. It has other functionalities beyond the scope of this paper, such as outdoor wireless communication, allowing use not only in conventional imaging rooms but also anywhere inside and outside hospitals. We believe that this system will enable digitalization in ﬁelds that have given it up and thereby reduce the workload of technicians and doctors in diagnosis of as many patients as possible. Trademarks ・ CALNEO Smart, CALNEO C and HYDRO AG referred to in this paper are trade names or registered trademarks of FUJIFILM Corporation. ・ Any other company names or system and product names referred to in this paper are generally their own trade names or registered trademarks of respective companies. FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 9 Development of a Next-generation CCD Imager for Life Sciences Research Seishi IKAMI*，Takashi KOBAYASHI**，Yasutake TANAKA*，and Akira YAMAGUCHI* Abstract We have developed a next-generation CCD-based imager with a new design concept for use in life sciences research. In this report, we describe the conﬁguration of the imager system and its features of high image quality, multifunctionality, and ease of use. This imager has been made commercially available as Amersham Imager 600 by GE Healthcare. 1. Introduction 2. System configuration Biochemistry and molecular biology research often uses image analysis techniques on the detected proteins with respective patterns that have been separated using gel electrophoresis and then labeled with chemiluminescent substrates and ﬂuorescent substances. There are two imaging modes employed in such analysis: imaging the gel itself that has undergone electrophoresis; and imaging a membrane to which proteins inside the gel are transferred using the western blotting method. The latter often utilizes chemiluminescent substrates but their luminescence is very weak; therefore, it requires a high-sensitivity, low-noise imaging system. In 1997, to meet that requirement, FUJIFILM developed the Luminescent Image Analyzer LAS-1000 that incorporated a large-aperture lens and a cooled CCD camera. Since then, the company has released the LAS series analyzers including LAS-3000 onto the market to respond to an extensive range of applications and has realized multifunctionality such as sensitivity enhancement and ﬂuorescence detection.1) In 2009, FUJIFILM formed a global alliance with GE Healthcare for the image analyzer business in the ﬁeld of life sciences2). Thereafter, the company has developed and manufactured CCD imagers, such as the ImageQuant LAS 4000 series and ImageQuant LAS 500, which have been distributed by GE Healthcare. In March, 2014, pursuing higher image quality, more advanced multifunctionality and usability, FUJIFILM launched onto the global market via GE Healthcare the CCDbased Amersham Imager 600 series (Fig. 1) developed with a new concept as the successor of the ImageQuant LAS 4000 series. This paper describes the system conﬁguration of the Amersham Imager 600 series and its features focusing on high image quality, advanced multifunctionality and usability. The Amersham Imager 600 series (hereinafter, the AI600 series ) provides imaging systems that incorporate the following features inside the housing: imaging unit consisting of a cooled CCD camera in combination with a large-diameter lens that is suitable for the high-sensitivity detection of weak chemiluminescence; imaging light sources and a ﬁlter; and a single-board computer that controls the operation of the preceding components. The imaging systems can be applied to a variety of uses, such as chemiluminescence detection using a gel and membrane, visible detection (colorimetric detection) and ﬂuorescence detection. The major Original paper (Received December 11, 2014) * Life Science Products Division FUJIFILM Corporation Akasaka, Minato-ku, Tokyo 107-0052, Japan 10 Fig. 1 Exterior appearance of Amersham Imager 600. ** Medical System Research & Development Center Research & Development Management Headquarters FUJIFILM Corporation Miyanodai, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8538, Japan Development of a Next-generation CCD Imager for Life Sciences Research speciﬁcations of the AI600 series are described in Table 1 and the outline of their internal structure is illustrated in Fig. 2. The AI600 series includes the following four imaging systems: AI600 that provides basic functions for chemiluminescence detection and colorimetric detection using white light epi-illumination; AI600UV that provides additional functions for ﬂuorescence detection utilizing UV optical excitation that is suitable for ethidium bromide (EtBr), etc.; AI600QC that provides further additional functions for optical density measurement in colorimetric detection using white light transillumination; and the fully-equipped AI600RGB that also provides functions for ﬂuorescence detection utilizing RGB optical excitation that is suitable for Cy dye, etc. Users can select any of the four types depending on the purpose. It is also possible to upgrade the current type to that with higher functionality by adding the necessary modules such as light source units. Fig. 2 Overview of the internal structure (AI600 RGB, side view). Table 1 Speciﬁcations FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 11 Each type of imager has two imaging positions, upper and lower. The tray containing samples (gel, etc.) is mounted onto either imaging position according to the application. The upper position is exclusively for chemiluminescence detection, allowing higher-sensitivity imaging than the lower position. In the lower position, imaging for all types of chemiluminescence detection, colorimetric detection and ﬂuorescence detection is available. The image capture size varies depending on the imaging position. However, in either position, the size per pixel on the image is the same and 300dpi or higher resolution, which is required for academic papers at submission, can be achieved. By deploying a UV transilluminator under the tray and white light transilluminators at the left and right sides under the tray, we have realized a system that does not require the exchange of transillumination units to suit each application (Fig. 3). In the case of using the UV transilluminator, a UV trans tray should be placed in the lower imaging position. Then, UV light from the UV transilluminator whose visible light components are blocked irradiates the ﬂuorescent dye sample placed on the tray. In the case of using white light transilluminators, a white trans tray should be placed in the lower imaging position after a white diffuser is placed over the UV transilluminator. Then, the light radiating toward the center from the white light transilluminators deployed at the left and right sides under the tray is scattered between the undersurface of the tray and the surface of the white diffuser. The scattered light illuminates the whole tray and thus irradiates the visible dye sample placed on the tray. In the AI600 series, we have realized smaller and lighter imaging systems than those of the ImageQuant LAS 4000 series (hereinafter, the LAS 4000 series ) by creating a compact transillumination unit as described and optimizing the positions of the LED epi-illuminator and CCD. The AI600 series imaging systems can be operated by the following three methods (Fig. 4). (1) Via a tablet PC connected using an ordinary USB wireless LAN adapter (2) Via a touch panel display connected using DVI and USB cables (3) Via the AI600 series imaging system itself emulating a PC with a monitor, keyboard and mouse connected using USB cables The imaging systems support virtual network computing (VNC) based on HTML5 technology, allowing operation and control via a Web browser on the tablet PC without the installation of special software. The tablet PC can be mounted onto the AI600 series imaging systems. Captured images can be saved to any of the following destinations. (1) Internal storage of the AI600 series imaging system (2) USB memory stick or USB-connected hard disk (3) PCs connected to the same network It is also possible for network PCs to retrieve the image data saved to the internal storage of the AI600 series imaging system by accessing a pre-installed Web application. 3. High image quality 3.1 Improved CCD driving method CCD cameras output signals even without any light input. Those signals are noise called dark current and cause the degradation of image quality, having lowered the signal to noise ratio (S/N ratio). Dark current has a large impact particularly when the exposure period is long because it keeps accumulating during the exposure period. Therefore, many imaging Fig. 3 Schematic view of the trans-illuminator. 12 Development of a Next-generation CCD Imager for Life Sciences Research Fig. 4 System connection diagram. AI600 can be operated by a tablet PC with a wireless LAN adapter. Fig. 5 Relationship between electrical noise and temperature. systems used in the ﬁelds of life sciences are designed so as to achieve a high S/N ratio by cooling their CCDs and thereby reducing dark current. On the other hand, noise can also occur during reading in CCDs and rear-stage circuits. The total noise of a CCD camera is the sum of the dark current noise and read noise (Fig. 5). The former noise is dominant at room temperature, while the latter is dominant when the CCD is cooled sufﬁciently. We therefore developed a new CCD driving method to reduce read noise for the AI600 series. The following is a description of the driving method when horizontal two-pixel binning is applied, referring to the example of CCD driving waveforms shown in Fig. 6. Resetting the CCD ejects electrical charges accumulated in the output stage FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 13 Fig. 6 CCD driving waveform and output signal (horizontal 2 pixel binning). and the CCD output signal settles to the reference potential (Vft). Next, a horizontal transfer clock falling edge causes the transferred charge of the ﬁrst pixel to create a corresponding change in the CCD output signal voltage. Then, another horizontal transfer clock falling edge, without the application of a reset, causes the transferred charge of the second pixel to create a further change in the CCD output signal voltage, achieving a ﬁnal potential value of Vdata. The difference of 14 potential between Vft and Vdata is proportional to the amount of light that has irradiated the two binned pixels. Read noise can be reduced by performing sampling multiple times (oversampling) when potentials Vdata and Vft are converted from analog to digital and calculating the average value. In the AI600 series, we shortened the time between the ends of the ﬁrst and second pixel transfers while extending the Vdata and Vft periods. In that way, we increased the sampling Development of a Next-generation CCD Imager for Life Sciences Research counts and reduced read noise. In addition, we optimized the CCD drive voltage and eventually achieved a 60% reduction of read noise compared with that before the improvement of the CCD driving method. 3.2 Spectrum optimization with excitation and fl uorescence fi lters Fig. 7 shows the excitation and ﬂuorescence emission spectra of the Cy series ﬂuorescent dyes. For example, when a sample containing Cy2 and Cy3 is irradiated by 500-nm light, both Cy2 and Cy3 dyes are excited. Therefore, inclusion of any Cy3 ﬂuorescence during the detection of Cy2 ﬂuorescence (crosstalk) prevents correct ﬂuorescence detection. The AI600RGB imaging system has a multiplex ﬂuorescence imaging function (see 4.3 for details), allowing the selection of the following light source-ﬁlter combinations suitable for Cy2, Cy3 and Cy5 dyes: 460-nm LED epi-illuminator and ﬂuorescence ﬁlter for Cy2 (525BP20); 520-nm LED epi-illuminator and ﬂuorescence ﬁlter for Cy3 (605BP40); and 630-nm LED epi-illuminator and ﬂuorescence ﬁlter for Cy5 (705BP40). Fig. 7 also shows the dominant wavelengths of the excitation light sources and the transmitted wavelength ranges of the ﬂuorescence ﬁlters over the spectrum. The 520-nm LED epi-illuminator for Cy3 detection is designed so it can excite Cy3, hardly overlapping the Cy2 excitation spectrum and the ﬂuorescence ﬁlter for Cy3 is designed so its transmission wavelength band allows Cy3 ﬂuorescence detection with little inﬂuence by Cy2 ﬂuorescence emission spectrum. The light sources and ﬁlters for Cy2 and Cy5 detection are designed according to the same concept. As described, the AI600RGB imaging system has realized ﬂuorescence detection with little crosstalk by employing optimized excitation light source and ﬂuorescence ﬁlter combinations. Fig. 7 Spectral characteristics: Excitation (ex.) and ﬂuorescence emission spectra (em.) of Cy dyes, and dominant wavelengths of the excitation light sources and emission ﬁlters of the AI600 series. 4. Multifunctionality 4.1 Semi-automatic exposure function The conventional automatic exposure function provided by the LAS 4000 series adjusts exposure automatically so the region emitting the most light on the whole image will achieve an optimal density. However, the target band is not always that region and there has been a request for imaging with a target band, even though emitting less light, at an optimal density. To meet that user need, we have incorporated into the AI600 series a semi-automatic exposure function, which allows users to specify a target band region via the window displaying the image (Fig. 8). With that function, it has become possible to automatically set an optimal exposure for the target band. Fig. 8 Semi-automatic exposure screen. FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 15 Fig. 9 Overlay image display 4.2 Color imaging and overlay function The LAS 4000 series employs unmodiﬁed grayscale CCDs. Therefore, they cannot reproduce the colors of bands stained with visible dyes or color molecular weight markers such as rainbow markers. However, the AI600 series imaging systems are equipped with LED epi-illuminators and transilluminators (QC and RGB types only) as white light sources for colorimetric detection that can light red, green and blue in turn via independent control, which enables color imaging even with grayscale CCDs. Colored visible light images of gels and membranes are reproducible with the AI600 series. In addition, the AI600 series incorporates a function to display and save data of colored visible light images overlaying chemiluminescence or ﬂuorescence grayscale images. By conﬁrming the colors of color molecular weight markers on the display window with that function, it is possible to visually estimate the molecular weight of the target band without difﬁculty (Fig. 9). 16 4.3 Realization of multiplex fluorescence imaging For the imaging of multiplex ﬂuorescent samples using multiple ﬂuorescent reagents, it is necessary to change the combination of ﬂuorescence excitation light sources and ﬂuorescence ﬁlters according to the reagents used. The conventional LAS 4000 series imaging systems ﬁrst perform a monochromatic ﬂuorescence imaging operation for each color and then analyze image data for those colors individually with separate analytical software. If necessary, they perform analysis after creating overlaid images on the analytical software. On the other hand, the AI600RGB imaging system has realized a function to carry out ﬂuorescence imaging for each color in a single automatic operation and obtain multiplex ﬂuorescence image data automatically. Because the imaging system can process a multi-color image data set simultaneously, it is also possible to conﬁrm and analyze multiplex ﬂuorescence images with the images overlaying each other (Fig. 10). Development of a Next-generation CCD Imager for Life Sciences Research Fig. 10 Multiplex ﬂuorescence image display. FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 17 Fig. 11 Schematic view of optical density measurement. Fig. 12 Relationship between the optical density on the chart [Remark 1] and measured optical density. 4.4 Optical density measurement function The AI600QC and AI600RGB imaging systems can measure the concentration of proteins stained with visible dyes quantitatively as an optical density with a high-sensitivity and simple method. The following is a description of the correction method used to increase quantitative performance. Detection signals obtained via the imaging of the stained proteins contain light components that were transmitted through the proteins (transmitted light to be measured) and diffracted light components that were transmitted through the gel surrounding the proteins (ambient light) (Fig. 11). Normally, the higher the protein concentration, the higher becomes the proportion of the ambient light to the total detection signals. That is an issue because that tendency causes the protein concentration to be underestimated. To solve that issue, we employed a correction method in which ambient light is removed from detection signals before measurement based on the pre-estimation of its inﬂuence. In that way, we have realized an imaging system that enables the high-precision measurement of protein concentration even in high optical density regions (Fig. 12). Fig. 13 Capture screens. 18 Development of a Next-generation CCD Imager for Life Sciences Research Table 2 Analytical functions Fig. 14 Analysis summary screen: Upper left: Image or proﬁle; Upper right: Graphs; Middle: Columns; Lower: Analysis workﬂow buttons 5. Usability 5.1 Intuitive GUI design The AI600 series employs intuitive, easy-to-understand graphical user interfaces (GUIs) so even ﬁrst-time users can smoothly operate the workﬂow of imaging, analysis and data saving. For example, as shown in Fig. 13, applications are grouped as Chemiluminescence, Colorimetric and Fluorescence, allowing the detailed setting of properties, such as exposure modes (Auto, Semi-auto, etc.) and light sources, separately for each application. For easy navigation of users, the buttons to move to the next operation, such as Next and Start, are uniformly blue with an easily visible size and are positioned at the bottom of the window. corporated analytical functions listed in Table 2. That allows users to carry out image analysis on the system without a break after the imaging of samples and the conﬁrmation of those images. In the analysis window, pressing the buttons at the bottom from left to right in sequence carries out analysis according to the workﬂow. When the analysis of the target band is over, a summary window is displayed as shown in Fig. 14, allowing the prompt conﬁrmation of analysis results. The analysis results can be saved and printed out. 6. Conclusion 5.2 Incorporation of analytical functions In the LAS 4000 series, analytical functions are provided by separate software. However, the AI600 series has the in- We have developed a next-generation CCD imager series for life sciences research called the Amersham Imager 600, based on the high-performance, high-reliability large-aperture lens and CCD already used in the ImageQuant LAS 4000 series and seeking even more advanced image quality, multifunctionality and usability. The new series comprises FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 19 four versions of imaging systems to respond to a variety of applications in chemiluminescence detection, colorimetric detection and ﬂuorescence detection, allowing the upgrade of the basic version to a higher-functionality version by adding modules such as light source units. To achieve higher image quality, we reduced noise with a new CCD driving method as well as crosstalk by optimizing ﬁlter spectra in ﬂuorescence detection. As part of the effort for advanced multifunctionality, we incorporated into the series a semi-automatic exposure function that enables the speciﬁcation of target band whose density can thereby be optimized; a color image overlay function that allows easy estimation of the molecular weight of a band via visual comparison with the color molecular weight marker; a multiplex ﬂuorescence imaging function that allows the assessment of images captured using multiple ﬂuorescent reagents, automatically overlaying each other; and an optical density measurement function that quantiﬁes the protein concentration of bands. Furthermore, for enhanced usability, we introduced intuitive GUIs for easy operation of the workﬂow of imaging, analysis and data saving and incorporated analytical functions to achieve seamless operation from imaging to analysis on the same system. References 1) Ikami, S. Development of a New Analyzing System for Life Science; Luminescent Image Analyzer LAS-3000 multi color . FUJIFILM Research & Development. 2005, no. 50, p. 39-44. 2) FUJIFILM News. 2009-05-28. http://www.fujiﬁlm.com/news/ n090528.html (accessed 2014-12-05). Trademarks ・ Company names or system and product names referred to in this paper are generally their own trade names or registered trademarks of respective companies. 20 Development of a Next-generation CCD Imager for Life Sciences Research Improvement in Image Quality and Workflow of X-Ray Examinations using a New Image Processing Method, “Virtual Grid Technology” Takahiro KAWAMURA*，Satoshi NAITO*，Kayo OKANO*，and Masahiko YAMADA* Abstract We have developed a new image processing method Virtual Grid Technology to improve the quality of degraded image due to scattered radiation. This technology improves the quality of images taken without an anti-scatter grid at bedside or emergency radiography. Conventionally, grids are commonly used to reduce the inﬂuence of scattered radiation. However, due to the positioning difﬁculties, images are often acquired without a grid for mobile examinations, which results in images with low contrast. Virtual Grid calculates the component of the scattered radiation from an image exposed without a grid and improves the contrast and granularity to replicate that of an image exposed with a grid. This technology resolves the problem of artifacts caused by misalignment when using a grid, and enables a more efﬁcient radiographic workﬂow. This report will describe an outline of Virtual Grid and explain its usefulness by using the experimental results. 1. Introduction The digitalization of X-ray radiography devices in the ﬁeld of general X-ray has been extended to mobile X-ray devices, and gradually extended to portable examinations at the bedside of hospitalized patients and in the NICU (Neonatal Intensive Care Unit). FUJIFILM released a cassette-type digital Xray diagnostic imaging unit D-EVO in 2010 to improve the image quality of portable radiography and to optimize the portable examination workﬂow using the immediacy of DR. Grid (a metallic ﬁlter made of lead strips), which removes scattered X-rays, is widely used in clinical settings since it improves image contrast. However, if X-rays penetrate to the grid at an oblique angle, uneven density appears on the resultant images. Especially in portable examinations where the grid is often slanted due to ﬂexture of the bed and other factors, uneven densities (Fig.1(a)) can be indistinguishable from changes in density caused by medical conditions, making image reading difﬁcult. For this reason, some medical facilities sometimes perform portable examinations without a grid although they understand that it may cause deterioration of image quality due to scattered X-rays (Fig.1(b)). Virtual Grid is an image processing technology that converts deteriorated image quality due to scattered X-rays (Fig.1(b)) to an improved quality image (Fig. 1(c)) by reducing the effect of scattered X-rays. 2. Virtual Grid Technology 2.1 Characteristics of Scattered X-Rays As shown in Fig. 2, X-rays of a subject can be largely classiﬁed into two types: primary X-ray that travels straight through the subject and is depicted as X-ray absorption according to the subject s anatomical structure, and scattered X-ray Fig. 1 Eﬃcacy of Virtual Grid Original paper (Received December 19, 2014) * Imaging Technology Center Research & Development Management Headquarters FUJIFILM Corporation Miyanodai, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8538, Japan FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 21 that changes its direction while travelling within the subject. Scattered X-rays change their characteristics according to a range of factors including the energy (radiation quality) of the irradiated X-ray, thickness of the subject and type of the subject (bone, muscle and/or fat). It is known that if the type of the subject and the size of the X-ray irradiation ﬁeld are the same, the amount of scattered X-rays will change depending on the thickness of the subject and the X-ray energy (radiation quality) 1). Fig. 3 shows the Scatter-to-Primary Ratio (STPR), the ratio of scattered X-rays to primary X-rays after penetrating the subject when the X-ray irradiation ﬁeld is set to be the same size as the X-ray detector. The STPR increases and image quality deteriorates as a subject gets thicker as the amount of scattered X-ray not contributing to the depiction of anatomical structure increases. 2.2 Virtual Grid Technology Virtual Grid consists of Contrast Improvement processing and Granularity Improvement processing to improve the decreased image contrast and the increased granularity caused by the scattered X-rays within the subject (Fig. 4). Below process ﬂow explains how "Scattered X-Ray Estimation" and "Grid Effect Calculation" processing combine to perform Contrast Improvement , and how "Noise Reduction" processing contributes for Granularity Improvement . Fig. 2 Primary and scattered X-rays Fig. 3 STPR vs. Thickness of subject Fig. 4 Process ﬂow of Virtual Grid Technology Fig. 5 Example method for estimating body thickness 22 Improvement in Image Quality and Workﬂow of X-Ray Examinations using a New Image Processing Method, Virtual Grid Technology 2.2.1 Scattered X-ray Estimation Processing As explained in the previous section, because the effect of scattered X-ray changes in accordance with the thickness of the subject, the scattered X-ray dose can be estimated by determining the thickness of the subject. The thickness of the subject can be estimated from the distance between the X-ray tube to the detector, as well as the exposure condition and the X-ray dose detected by the detector as shown in the example in Fig. 5. First, Scattered X-ray Estimation processing estimates the X-ray dose on the surface of the detector and the distance between the X-ray tube and the detector from the exposure condition which was taken without a subject (a). Secondly, the X-ray dose immediately after penetrating the subject (b) is calculated from the pixel value of the observed image. Finally, the image processing calculates the X-ray dose absorbed by the subject using the values (a) and (b) to estimate the thickness of the subject. 2.2.2 Grid Effect Calculation Processing When a grid is used, the X-ray signal immediately after penetrating a subject is reduced according to the primary and scatter transmission factors of the grid before it is observed by the detector. Virtual Grid replicates this action through Fig. 6 Grid eﬀect calculation calculations. An overview of Grid Effect Calculation processing is explained by using Fig. 6 below. As mentioned in the previous section, the Scattered X-ray Estimation processing can calculate the component of the scattered X-ray included in the X-ray signal immediately after penetrating a subject, and the X-ray signal can be observed in the resultant image and as the consequence, the primary X-ray component in the signal immediately after penetration can be calculated. The primary and scattered X-ray signal after the grid can then be calculated using the primary and scattered X-ray signal immediately after penetrating the subject as well as the primary and scatter transmission factors of the grid. In other words, an image similar to that exposed with a grid can be obtained by calculation as long as the primary X-ray dose and the scattered X-ray dose immediately after penetrating a subject are properly estimated. 2.2.3 Granularity Improvement Processing The X-ray reaching the detector consists of the primary Xray components, which have structures such as lines and dots, and the scattered X-ray components, which do not have any structure. Structure-less X-ray signal, which is contained in the scattered X-ray signal, increases the X-ray quantum noise within the image. With Granularity Improvement processing, the granularity of an image is improved by extracting and reducing the component of structure-less noise . An outline of the Granularity Improvement processing is shown in Fig. 7. In order to extract the noise components, this processing recognizes not only simple dot and line structures, but also recognizes more complex structures such as cross shaped and T shaped line structures. Using the results of this recognition, a ﬁlter is applied to structure-less regions to reduce noise components. As for structured region, applying ﬁlters with different characteristics according to the structure pattern reduce the noise components included even in dot and line structures. Fig. 7 Granularity improvement FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 23 Fig. 8 Eﬀect of granularity improvement (magniﬁed) The result of the Granularity Improvement processing applied to a clinically exposed image of the chest region is shown in Fig. 8. The granularity of the image with Granularity Improvement processing applied (Fig. 8(c)) has been dramatically improved compared to the image before processing has been applied (Fig. 8(a)). Moreover, because the subject structure is not visible in the image after the noise component is reduced, (Fig. 8(b)), it is clear that the Granularity Improvement processing does not deteriorate the signal component. 3. Quantitative Assessment using Physical Indicators ※1 3.1 Contrast As shown in Fig. 9, contrast is measured using an acrylic physical phantom with a thickness of 1 cm. In order to simulate different body types, physical phantoms were exposed after being sandwiched between acrylic scattering objects. Contrast is deﬁned as the difference between the average density (a) of the base section of the physical phan- tom and the average density (b) of the air hole section. The measurement results are shown in Fig. 10. The horizontal axis of the graph represents the total thickness of the acrylic objects that sandwich the phantom while the vertical axis of the graph represents the physical phantom contrast. The graph shows that the Virtual Grid calculates different scattered X-rays according to the thickness of the subject and is effective in improving contrast to the same level as when a grid is used. 3.2 Granularity The measurement results of granularity using an acrylic physical phantom are shown in Fig. 11. As the comparison is based on the thickness of the subject, the irradiation dose for exposures is set such that the dose after penetrating the subject becomes constant (5 mR). The horizontal axis of the graph represents the thickness of the acrylic objects which the physical phantom is being sandwiched. The vertical axis of the graph represents the RMS (Root Mean Square) granularity of the physical phantom pixel values. The higher the value on the vertical axis, the worse the granularity. Because Granularity Improvement processing of the Virtual Grid shows smaller RMS granularity values than those of images exposed with a grid, it is clear that this technology can signiﬁcantly improve granularity. Fig. 9 Study condition using contrast phantom Fig. 10 Contrast improvement by Virtual Grid ※1 24 Fig. 11 Granularity improvement by Virtual Grid Because the scattering medium used in the physical measurement is made of acrylic and differs from the human body, we used physical parameters suitable for the material. Further, the X-ray tube was calibrated such that a dose reaching the detector becomes 7.2 mR under the designated exposure conditions (80 kV, 1 mAs, 100 cm). We use a DR flat panel x-ray detector FDR D-EVO 14x17” GOS (G35i) in this test. The equipment used was FUJIFILM DR CALNEO C 1417. Improvement in Image Quality and Workflow of X-Ray Examinations using a New Image Processing Method, “Virtual Grid Technology” The improvement of the image quality is shown as the Contrast-to-Noise Ratio (CNR). The relationship between the thickness of the subject and CNR is presented in Fig. 12. When CNR for the images exposed with a grid is compared to that of the images exposed without a grid, CNR for images without a grid is higher in thin areas where there are a lot of primary X-rays. Similarly, the CNR for images exposed with a grid is higher in thick areas where there are many scattered X-rays. This relationship shows that, the thicker the subject, the greater the improvement beneﬁt in image quality from the grid. We can see that for all thicknesses, the CNR for images exposed with the Virtual Grid is higher than that for images exposed with a grid. 3.3 Sharpness For sharpness, the MTF (Modulation Transfer Function) is measured with an edge method2) using a Tungsten edge with a thickness of 1 mm. In order to measure the sharpness of a structure within the subject, the Tungsten edge was exposed after being sandwiched by acrylic scattering objects as shown in Fig. 13. For images exposed with a grid, the grid and edge were placed where the grid pattern and the edge were set at a right angle. Further, sharpness of subjects in various thicknesses was measured by changing the thickness of the acrylic. The measurement results are shown in Fig. 14. The horizontal axis of the graph represents the spatial frequency and the vertical axis of the graph represents the MTF; showing that the higher the value, the greater the level of sharpness. At any subject thickness, the sharpness of the images exposed with the Virtual Grid was at the same level as those without the Virtual Grid. Further, even when the thickness of the subject was increased, the sharpness was at almost the Fig. 12 CNR improvement by Virtual Grid Fig. 13 Study condition for sharpness measurement Fig. 14 Sharpness of Virtual Grid Fig. 15 Quantiﬁcation of image quality by CDRAD phantom FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 25 same level, indicating that there was virtually no degradation in high frequency sharpness due to scattered X-rays. 3.4 Signal Detection Capability We compared the signal detection capability of images processed with Virtual Grid to that of images exposed with grids. Signal detection capability was automatically calculated using Artinis Medical Systems CDRAD 2.0 phantom and its analysis software V2.1 3). As shown in Fig. 15, there is one hole in the middle and another hole in a corner within each grid on the acrylic of a CDRAD phantom. The size and depth of a set of holes vary in each square. In an evaluation using a CDRAD phantom, by identifying the positions of holes in all squares, the CD curve showing the visibility range is described and IQF inv, the index value of image quality, is calculated. This index is simply calculated by using the analysis software of the same company. IQF inv is an index that the total image quality including the contrast and granularity has been quantiﬁed. The higher IQF inv leads to the higher image quality which means that the image can depict smaller, lower contrast signals. As indicated in Fig.16, a 1 cm-thick CDRAD phantom was Fig. 16 Study conditions using CDRAD phantom Fig. 18 Contrast detail curve (3.6 mAs) 26 placed between PMMAs, which each of them has the thickness of 5 cm under two conditions: The condition A with two PMMAs (10 cm) and the condition B with four PMMAs (20 cm) assuming exposure to a human body were chosen for the study. Fig. 17 shows the relation between the exposure dose and the relative IQF inv. In the relative IQF inv, 3.6 mAs in the condition A and 10 mAs in the condition B were normalized as the IQF inv value of 1 . According to Fig. 17, the relative IQF inv without a grid is lower than with a grid and the image quality was assumed to be reduced due to scattered X-ray. However, it shows that applying the Virtual Grid indicates higher relative IQF inv value at any exposure condition than when a grid was used. Since the above can be conﬁrmed in the conditions A and B with the various thicknesses of PMMAs, it can be said that the Virtual Grid has an effect of improving the image quality at least up to the condition B. Fig. 18 shows a CD curve at 3.6 mAs under the condition A. Compared to images exposed with a grid, smaller Fig. 17 Calculation results of IQFinv Fig. 19 Contrast detail curve (1.8 mAs) Improvement in Image Quality and Workflow of X-Ray Examinations using a New Image Processing Method, “Virtual Grid Technology” Fig. 20 Image comparison (anti-scatter grid vs. Virtual Grid) and lower contrast signals are rendered in images obtained using the Virtual Grid, and it can be conﬁrmed that signal degradation does not occur during the Granularity Improvement processing. Further, Fig. 19 shows a CD curve for a case in which the exposure without a grid is performed at 1.8 mAs for comparison with a CD curve at 3.6 mAs under the condition A. It is clear that by using Virtual Grid, image quality is improved even with images obtained through lowdose exposure. Reference 1) Bushberg, J. T.; Seibert, J. A.; Leidholt, E. M.; Boone, J. M. The Essential Physics of Medical Imaging. Williams & Wilkins, 1994, 742p. 2) Samei, E.; Flynn, M. J.; Reimann, David A. A method for measuring the presampled MTF of digital radiographic systems using an edge test device. Medical Physics. 1998, 25 (1), p.102-113. 3) Pascoal, A.; Lawinski, C. P.; Honey, I.; Blake, P. Evaluation of a software package for automated quality assessment of contrast 4. Results of application to images of the human body The results of applying Virtual Grid to images of the human body are shown in Fig. 20. Fig. 20(b) shows a low-dose image to which the Virtual Grid was applied. It has nearly the same level of contrast as the image in Fig. 20 (a), which was exposed with a grid. In the enlarged view comparison, we can conﬁrm that the details of anatomical structures such as pulmonary vessels, ribs, and the heart are close to those of grid exposure images, and that even in terms of sharpness and granularity, the Virtual Grid provides image quality comparable to that acquired with grid exposure. detail images-comparison with subjective visual assessment. Physics in Medicine and Biology. 2005, 50 (23), 5743. Trademark ・ FUJIFILM and D-EVO in this document are registered trademarks of Fujiﬁlm Corporati ・Any other company names or system and product names referred to in this paper are generally their own trade names or registered trademarks of respective companies. 5. Summary We have explained the priniciples of image improvement achieved through the newly developed Virtual Grid in comparison to conventional grid methods. We have also veriﬁed through physical experiments that the use of this technology can improve the contrast degradation and granularity caused by scattered X-rays, enhancing image quality. We anticipate broad applications of this technology to contribute in improving both image quailty and workﬂow, and we intend to continue developing technology that will lead to further improvements in the quality of medical care in future. FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 27 Quantification of the Respiratory Activity of the Lung using CT Images Takayuki HASHIMOTO*，Caihua WANG**，and Jun MASUMOTO* Abstract We have developed a system to analyze the respiratory activity of the lung using CT images. This analysis includes functions to automatically extract the lung region from several phases of chest CT images, register the different respiratory phases, and obtain a motion vector ﬁeld. This enables an overlay display of the low attenuation areas, the quantiﬁcation of the expansion rate of the lung, and the measurement of local movement. With these functions, we can visualize the local respiratory activity, which was previously difﬁcult to observe. Using this system, we hope to obtain indicators that are effective for studying the areas from which respiratory diseases originate, their severity, and their causes. 1. Introduction In recent years, there has been a trend in the medical ﬁeld for the spread of imaging systems, such as computed tomography (CT) and magnetic resonance (MR), the improvement of imaging techniques used with them and the establishment of intra-hospital infrastructure for picture archiving and communication systems. The use of 3D medical images has been increasing not only in radiology departments but also in clinical domains such as surgical departments and departments of internal medicine. Under such circumstances, in 2008, FUJIFILM released the 3D-imaging diagnostic workstation SYNAPSE VINCENT※1 developed based on its long-cultivated, advanced image processing technology. In addition to a variety of analytical functions to support image interpretation for radiology departments that make diagnoses via images, the product also features surgical simulation functions with 3D medical images for the surgical area where treatment is provided to patients. In particular, it is widely used at actual clinical sites in the simulation of partial liver resection. Recently, it has also provided, for the domain of respiratory organs, functions to support diagnosis of lung disease (cancer, chronic maladies, pulmonary emphysema, etc.) with CT images and surgical simulation functions using technology that allows the automatic image extraction of pulmonary arteries, pulmonary veins and bronchi from contrast-enhanced CT images of the lung. ※1 On the other hand, for the diagnosis of the respiratory function in internal medicine, it is an important factor to identify the capacity of pulmonary ventilation associated with the respiratory activity of the lung; therefore, in addition to the identiﬁcation of diseased regions inside the lung, the identiﬁcation of its severity and cause has also been a subject of research in diagnostic methods. This paper reports new technology for dynamic analysis of the lung with CT images that is expected to become a future image diagnostic method for the respiratory function. 2. Conventional methods for the diagnosis of the respiratory function There are many diseases treated by respiratory medicine including chronic obstructive pulmonary disease (COPD),1) pulmonary embolism (PE) and interstitial pneumonia (IP) and diagnosis requires very speciﬁc and deep knowledge. In particular, COPD is one of the most fatal diseases in the world and the number of patients who suffer from that disease has been increasing.2), 3) The disease is classiﬁed minutely according to the cause, such as pulmonary emphysema due to alveolar collapse and chronic bronchitis due to airway obstruction. However, the cause is often complex and correct diagnosis is not at all easy. The following are the currently typical diagnostic methods for the respiratory function of the lung. SYNAPSE VINCENT is the product name of the Fuji Imaging Diagnostic Workstation FN-7941 (Pharmaceutical Aﬀairs Authentication No. 22000BZX00238000). Original paper (Received November 27, 2014) * Medical System Research & Development Center ** Imaging Technology Center Research & Development Management Headquarters Research & Development Management Headquarters FUJIFILM Corporation FUJIFILM Corporation Nishiazabu, Minato-ku, Tokyo Nishiazabu, Minato-ku, Tokyo 106-8620, Japan 106-8620, Japan 28 Quantification of the Respiratory Activity of the Lung using CT Images 2.1 Pulmonary function test (spirometry) This method can be regarded as a de facto standard in the diagnosis of the respiratory function currently practiced, in which diagnosis is made by having patients actually take a series of breathing activities: taking a big breath and exhaling it. With this method, it is possible to make some assessment on the respiratory function of the lung as a whole but speciﬁc malfunctioning regions cannot be identiﬁed. 2.2 Diagnosis with CT images (inflated lung) Diagnosis is made using chest CT images based on the distribution of signal values inside the lung ﬁeld. Generally, regions occupied by air whose alveoli are ﬂat have low signal values and their respiratory function is considered to have decreased. Therefore, it is possible to assess the function of the lung by identifying the distribution of those regions. However, although allowing the identiﬁcation of diseased regions and sometimes their severity, this method cannot identify the cause. 2.3 Diagnosis with SPECT images Diagnosis is made based on images that capture the state of radioisotopes (RIs), such as 81mKr and 133Xe gases, staying inside the alveoli after inhalation by patients (single photon emission computed tomography, SPECT images). However, the resolution of those images is low and they can only give general information about the condition of pulmonary ventilation. Diagnosis with this method requires higher interpretation skills and longer examination time than other methods. 3. Mechanism of dynamic analysis of the lung The new method we are now going to introduce enables more detailed, quick diagnosis than conventional methods by analyzing the movement of the lung itself with CT images captured at multiple phases of the respiratory activity. The technique supports the diagnosis of pulmonary ventilation capacity in the respiratory activity via the high-precision registration of multi-phase CT images incorporating anatomical knowledge (e.g., the shape of the lung, positions of the bronchi) and observation of the detailed lung transformation data. 3.1 Registration technology First, to calculate the pulmonary ventilation function of each region, it is necessary to correctly determine the movement of the detailed anatomical structures of the lung captured in CT images at its maximum inspiration and at expiration at rest. To that end, we developed a new non-rigid registration method by incorporating our long-cultivated image processing technology into conventional registration methods.4), 5) The procedures are as follows: let either CT image at maxi- FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) mum inspiration or at expiration at rest be a ﬁxed image; let the other image be a moving image; transform the moving image while applying non-linear transformations; calculate the metric (degree of similarity) between the ﬁxed image and the transformed moving image; determine the transformation when the metric becomes highest by repeating the preceding two procedures; and let it be the optimal transformation between the ﬁxed and moving images (Fig. 1). By using the determined optimal transformation, the correspondence of all the voxels between the ﬁxed and moving images can be obtained, based on which, it is possible to calculate the movement of any region of the lung between maximum inspiration and expiration at rest. Fig. 1 Mechanism for the registration of the images 3.2 Visualization of the registration results This system performs the mapping of voxels based on the registration results and visualizes the differences of signal values between images, thus allowing the conﬁrmation of the precision of registration. There is a signiﬁcant difference between the signal values of a blood vessel or bronchus and those of the lung ﬁeld. Therefore, a deviation in registration appears as an obvious difference in color intensity in the difference image. That means, the more even the color intensity in the difference image, the more accurate and normal the registration results are. Fig. 2 shows difference images. Fig. 2 (a) is a difference image obtained by subtracting the raw signal values of the expiration image from the inspiration image, while (b) is a Fig. 2 Diﬀerence image 29 Fig. 3 Diﬀerence image difference image obtained by subtracting the signal values of the expiration image after automatic registration from the inspiration image. In the former image, deviations of the lung ﬁeld and blood vessels are represented in intense white or black. In the latter, the lung ﬁeld is the same ﬂat color and the blood vessels and bronchi are edged by the difference in color intensity around their outlines. That is because each tissue has shrunk due to the difference in pressure of the lung ﬁeld during the respiratory activity. If edges are detected in the same way at both ends of each vascular channel, it means the position of the center line is correctly registered (Fig. 3). Should there be any anatomical deviation in the results of automatic calculation for registration, higher-precision results can be obtained by manually specifying a more characteristic position with the same anatomical structure in both ﬁxed and moving images and applying registration again. 4. Quantification of the respiratory activity of the lung There are two criteria in the assessment of the respiratory function. One is whether the lung ﬁeld and blood vessels can physiologically circulate air via the alveoli. Another is whether air itself inside the lung ﬁeld is replaced with new air. The respiratory function is quantiﬁed and visualized by calculating voxel-level changes in signal values and movement based on the correspondence between images obtained from the registration results. 4.1 Display of low attenuation areas In the case of emphysematous lung disease, low attenuation areas (LAAs), which have low image signal values compared with those of the normal lung ﬁeld, appear in the inspiration image. For the detailed quantitative diagnosis of that type of disease, such as masurement of the percentage of LAAs inside the lung ﬁeld, Goddard classiﬁcation to assess its severity and cluster analysis6) to identify the extent of progress and region of the disease. On the other hand, the LAAs in the expiration image represent a phenomenon in which air inside the lung ﬁeld stagnates due to the narrowed bronchiole (air trapping). The phenomenon is considered to derive from peripheral airway lesions, for which there is a technology to analyze the proportion of stenosis using the internal and external diameters of the respiratory tract. As described, different ﬁndings can be obtained via the observation of images of different imaging phases. There is also a research paper reporting that combining the LAAs of the inspiration image with those of the expiration image is useful for the classiﬁcation of COPD.7) We therefore incorporated into this system a function utilizing the registration results that allows the observation of the regions where the LAAs of the inspiration and expiration images overlap each other as well as the individual observation of those LAAs. Fig. 4 (a) shows the display results of the LAAs of the inspiration image, while Fig. 4 (b) shows the LAAs of the expiration image corresponding to those of the inspiration image based on the registration results. Fig. 4 (c) provides the results of overlapping images (a) and (b) and distinguishing with different colors the LAAs of the inspiration image and of the expiration image, and those common to both images. Fig. 4 LAA display 30 Quantification of the Respiratory Activity of the Lung using CT Images Fig. 5 Moving line Fig. 6 Expansion rate per unit area 4.2 Visualization of movement The constriction of the lung is not a simple radial movement from its center to the surface. The movement is characteristic. For example, near the surface, it occurs as if sliding toward the ribs and, the nearer to the diaphragm, the larger it becomes. Therefore, by visualizing the movement of the lung, it becomes possible to compare the diseased lung with the normal one as well as to identify regions that are abnormal in local movements. This system can visualize the movement of the lung that occurs between the inspiration and expiration images based on the registration results. In addition, it can measure the travel of each individually speciﬁed region. Fig. 5 shows the results of representing the movement of the lung with lines. The direction and length of the lines indicate the horizontal movement of the lung. Vertical movement is visualized by coloring the lines according to the direction and signiﬁcance of the movement. The ﬁgure was obtained via calculation with the reference position for movement measurement (point of zero of travel) set to the center of gravity of the lung ﬁeld. FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 4.3 Visualization of the expansion rate Air inside the lung ﬁeld is exchanged mainly by the constriction of the diaphragm and intercostal muscle. Any defects in respiration weaken the constriction of the lung. There is also a possibility of the constriction being partially inhibited between the inspiration and expiration images if there is any air stagnation due to air trapping as described previously. Therefore, the observation of the expansion rate of the lung ﬁeld is useful in the diagnosis of pulmonary ventilation capacity. The left and right lungs are divided into ﬁve lobes in total. By taking into consideration those sections, it becomes possible to observe pulmonary ventilation capability section by section. This system can calculate and visualize the expansion rate for each speciﬁed region based on the registration results. Fig. 6 is a representation of the expansion rate of the inspiration image. Because it indicates the expansion rate at inspiration relative to expiration, the blood vessels and bronchi are not expanded, while the whole lung ﬁeld is. That differentiates the color of the blood vessels and bronchi from the lung ﬁeld, enabling the conﬁrmation of shape. 31 Trademarks 5. Conclusion We developed a 3D imaging diagnostic system with a new technology for dynamic analysis of the lung. The system visualizes the movement of the lung with CT images and thereby supports the identiﬁcation of diseased regions inside the lung and the diagnosis of their severity and causes. We are planning not only to add even more new lung-ﬁeld analytical functions but also to improve the system so it can also perform dynamic analysis of the bronchi. We will keep striving for the further advancement of SYNAPSE VINCENT, hoping that it will become a core system in the diagnosis and treatment of respiratory diseases, such as COPD, by being widely spread to clinical ﬁelds of respiratory medicine. ・ SYNAPSE VINCENT referred to in this paper is a registered trademark of FUJIFILM Corporation. ・ Any other company names or system and product names referred to in this paper are generally their own trade names or registered trademarks of respective companies. References 1) Guidelines for the Diagnosis and Treatment of COPD (Chronic Obstructive Pulmonary Disease), 2nd edition. Committee for the Second Edition of the COPD Guidelines of The Japanese Respiratory Society. 2004, p.137. 2) Ministry of Health, Labour and Welfare. Demographic Survey. http://www.mhlw.go.jp/toukei/list/81-1.html, (accessed 2014-11-25). 3) World Health Organization. World Health Statistics 2008 . http://www.who.int/gho/publications/world_ health_statistics/ EN_WHS08_Full.pdf, (accessed 2014-11-25). 4) Mattes, David; Haynor, David R.; Vesselle, Hubert; Lewellyn, Thomas K.; Eubank, William. Nonrigid multimodality image registration. SPIE Proc. 2001, Medical Imaging 2001: Image Processing, 4322, p.1609‒1620. 5) Cao, Yan; Miller, M.I.; Winslow, R. L.; Younes, L. Large deformation diffeomorphic metric mapping of vector fields. IEEE Transactions on Medical Imaging. 2005, 24(9), p.12161230. 6) Mishima, M.; Hirai, T.; Itoh, H.; Nakano, Y.; Sakai, H.; Muro, S.; Nishimura, K.; Oku, Y.; Chin, K.; Ohi, M.; Nakamura, T.; Bates, J. H.; Alencar, A. M.; Suki, B. Complexity of terminal airspace geometry assessed by lung computed tomography in normal subjects and patients with chronic obstructive pulmonary disease. Proc. Nat. Acad. Sci. U. S. A. 1999, 96(16), p.8829‒8834. 7) Albán, Craig J.; Han, Meilan K.; Boes, Jennifer L.; Chughtai, Komal A.; Meyer, Charles R.; Johnson, Timothy D.; Galbán, Stefanie; Rehemtulla, Alnawaz; Kazerooni, Ella A.; Martinez, Fernando J.; Ross, Brian D. Computed tomography-based biomarker provides unique signature for diagnosis of COPD phenotypes and disease progression. Nature Medicine. 2012, 18(11), p.1711‒1715. 32 Quantification of the Respiratory Activity of the Lung using CT Images Development of Quantitative Immunoassay Reagent “FUJI DRI-CHEM IMMUNO AU Cartridge vc-TSH and v-COR” Hiroyuki CHIKU*，Junichi KATADA*，Tomoya OHARA*，Noriyuki KASAGI*，Atsuhiko WADA*， and Kentaro NAKAMURA* Abstract We have successfully developed and commercialized the FUJI DRI-CHEM IMMUNO AU Cartridge vc-TSH and v-COR , which is a quantitative immunoassay system for the measurement of the thyroid stimulating hormone (TSH) and cortisol (COR) in dog serum. Last year, we developed the FUJI DRI-CHEM IMMUNO AU Cartridge v-T4 for the measurement of the thyroid hormone (T4). We have succeeded in providing a highly accurate diagnostic method for hypothyroidism in dogs by measuring T4 and TSH together. Furthermore, a rapid and simple method for diagnosing Cushing s syndrome in dogs was achieved by measuring COR. In addition to the competitive method, we have constructed a reaction system using the sandwich method and introduced dilution measurements. 1. Introduction The recent development of veterinary medicine has achieved great success in dramatically extending the average lifespans of pets. On the other hand, it has revealed that the existence of various types of disease due to aging among them. One of the most typical diseases is an endocrine disorder deriving from abnormal hormone secretion, such as, in the case of dogs, hypothyroidism related to the thyroid gland in the neck and Cushing s syndrome related to the adrenal glands neighboring the kidneys. In diagnosis, the blood concentrations of a thyroid hormone called thyroxine (T4) and thyroid-stimulating hormone (TSH) are utilized for the former disease, while the blood concentration of a cortical hormone called cortisol (COR) is utilized for the latter. However, many veterinary clinics entrust hormone tests to external inspection organizations and that prevents veterinarians from immediately starting treatment because it takes several days to obtain the results. Therefore, there was a demand for compact, rapid inspection systems that allow those tests inside the clinics. Last year, to respond to that need, we developed a quantitative T4 immunoassay reagent for veterinary use, FUJI DRI-CHEM IMMUNO AU Cartridge v-T4 (hereinafter, the FDC v-T4 ), and the dedicated analyzer, FUJI DRI-CHEM IMMUNO AU10V, and published a report about them.1) We introduced into that system surface plasmon-enhanced ﬂuorescence (SPF) technology as its principle for the detec- tion of ﬂuorescent particle labels because, with the conventional epiﬂuorescence method, the laser beam from above illuminates not only ﬂuorescent particles bound via immunoreaction but also isolated ones and washing is thus necessary to remove unreacted ﬂuorescent particles. In the SPF method, a thin metal ﬁlm bound with ﬂuorescent particles is irradiated from below with the laser beam with its incidence angle adjusted. That generates near-ﬁeld light via surface plasmon resonance (SPR), causing only ﬂuorescent particles bound onto the surface of the thin metal ﬁlm to emit light (Fig. 1). Because the method does not require a washing process, an assay takes only about ten minutes. In addition, without the necessity of washing solution and water discharge equipment, the system has realized signiﬁcant size reduction while featuring simple operation involving just loading the sample, cartridge and consumables into the system, then pressing the Start button (Fig. 2). In general, to assay antigens such as hormones, there are two immunoassay methods using the immunoreaction of antibodies. In the case of antigens whose molecular weight is tens of thousands of Da (e.g., TSH), the sandwich method is employed, in which antigens are sandwiched by two antibodies. In the case of antigens whose molecular weight is 1,000 Da or lower (e.g., T4, COR) and that cannot be sandwiched by antibodies, the competitive method is employed, in which antigen markers and antigens within the sample are made to compete for immunoreaction. In this paper, we report the outline of the technology and Original paper (Received December 15, 2014) * Pharmaceutical & Healthcare Research Laboratories Research & Development Management Headquarters FUJIFILM Corporation Ushijima, Kaisei-Machi, Ashigarakami-gun, Kanagawa 258-8577, Japan FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 33 clinical performance of the two new assay items we developed: FUJI DRI-CHEM IMMUNO AU Cartridge vc-TSH (hereinafter, the FDC vc-TSH ) using the sandwich method and FUJI DRI-CHEM IMMUNO AU Cartridge v-COR (hereinafter, the FDC v-COR ) that has realized a wide dynamic assay range by enabling dilution measurement of samples with the competitive method. 2. Development of the FDC vc-TSH using the sandwich method 2.1 Signifi cance of the TSH assay TSH is among the hormones secreted by the adenohypophysis. Its blood concentration is controlled by interaction between the hypothalamus, hypophysis and thyroid as follows. Inﬂuenced by TSH, the thyroid increases the secretion of thyroid hormones: thyroxine (T4) and triiodothyronine (T3). The a) Epiﬂuorescence method Laser beam Noise adenohypophysis secrets TSH, stimulated by thyrotropinreleasing hormone (TRH) secreted from the hypothalamus. At the same time, the secretion of those hormones is inhibited via negative feedback that occurs upon an increase of the concentrations of T4 and T3 in the blood. In that way, the secretion of the thyroid hormones is regulated (Fig. 3).1) Dog serum TSH is utilized in assays for the diagnosis of dog hypothyroidism in combination with dog serum T4. When the thyroid function is impaired, T4 secretion decreases. Therefore, it is known that many dogs suffering from hypothyroidism have a low serum T4 concentration, while showing a high serum TSH concentration because more TSH is secreted to increase T4. In diagnosis, the concentration of serum T4 is mainly used. However, that concentration may be inﬂuenced by other diseases. Using serum T4 concentration in combination with serum TSH concentration in assays can increase the precision of diagnosis.1) b) SPF method Detection of ﬂuorescence Detection of ﬂuorescence Washing is necessary. Laser beam Light from the upper surface illuminates not only bound but also isolated particles. Washing is thus necessary. Thin gold ﬁlm Isolated particles do not glow, so no washing is necessary. Fig. 1 Schematic drawings of the a) epiﬂuorescence and b) SPF methods. Immunoassay analyzer for veterinary use FUJI DRI-CHEM IMMUNO AU10V Thyroid-stimulating hormone (TSH) assay reagent FUJI DRI-CHEM IMMUNO AU Cartridge vc-TSH Cortisol assay reagent FUJI DRI-CHEM IMMUNO AU Cartridge v-COR [Measurement method] Sample Cartridge ・・・ Tip Load a sample, cartridge and tip. Press the Start button. Fig. 2 Quantitative immunoassay system for the measurement of TSH and COR in dog serum. 34 Development of Quantitative Immunoassay Reagent FUJI DRI-CHEM IMMUNO AU Cartridge vc-TSH and v-COR Hypothalamus Thyrotropin-releasing hormone TRH Adenohypophysis Thyroid-stimulating hormone Thyroid hormones TSH T4 T3 Stimulation Inhibition Thyroid Fig. 3 Negative feedback mechanism for the adjustment of thyroid hormones. 2.2 Principle of the assay with the FDC vc-TSH The TSH assay using the sandwich method is carried out as follows (Fig. 4). (1) The serum sample is dispensed into the reaction cup, which triggers a reaction between anti-TSH monoclonal antibodies labeled with ﬂuorescent particles (hereinafter, ﬂuorescent particle-labeled anti-TSH antibodies ) and TSH contained in the sample [Step 1]. At that time, the quantity of TSH bound to the antibodies on the ﬂuorescent particles increases in proportion to the TSH concentration of the sample. (2) The reaction solution is infused into the immunoreaction channel. Anti-TSH monoclonal antibodies (hereinafter, anti-TSH antibodies ) ﬁxed onto the thin gold ﬁlm formed inside the channel cause ﬂuorescent particle-labeled anti-TSH antibodies to be captured onto the ﬁlm in proportion to the quantity of TSH bound [Step 2]. Based on the amount of ﬂuorescence obtained via the SPF method, the system performs automatic conversion to TSH concentration and the assay results are thus obtained. 2.3 Main feature of the development of the reaction system : Inhibition of pseudoreaction in the sandwich method Immunoreaction systems that utilize antigen-antibody reactions are subject to measurement errors due to nonspeciﬁc reaction. In particular, the sandwich method suffers the problem of pseudoreaction by nonspeciﬁc reaction contributors, such as heterophile antibodies that exist in the serum sample. When heterophile antibodies exist in the serum sample, antibodies labeled with ﬂuorescent particles will be bound to those ﬁxed onto the thin gold ﬁlm via the heterophile antibodies and that is detected as ﬂuorescence signals. There is a concern that, as a result, abnormally high values may be obtained. Immunoreaction channel (Anti-TSH antibodies ﬁxed on the thin gold ﬁlm) TSH Fluorescent particle-labeled anti-TSH antibodies Solution infusion Thin gold ﬁlm Anti-TSH antibodies Amount of ﬂuorescence Reaction cup (Fluorescent particle-labeled anti-TSH antibodies) TSH concentration Fig. 4 Principle for measuring TSH in dog serum using FDC vc-TSH. Without nonspeciﬁc adsorption inhibitor Abnormally high values With nonspeciﬁc adsorption inhibitor No abnormally high values observed CLEIA method [ng/mL] CLEIA method [ng/mL] Fig. 5 Eﬀect of inhibition of a nonspeciﬁc reaction. FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 35 To resolve that problem, we developed a new nonspeciﬁc reaction inhibitor that absorbs nonspeciﬁc reaction contributors. The use of the inhibitor improved the results for the serum sample that indicated abnormally high values when chemiluminescence enzyme immunoassay (CLEIA), which was usually used by veterinary inspection centers, was employed as a control method (Fig. 5). 2.4 Clinical performance (1) Conﬁrmation of correlation To verify the effectiveness of the newly developed FDC vcTSH, we conﬁrmed correlation in dog serum using CLEIA as a control method. The FDC vc-TSH, with a correlation coefﬁcient (r) of 0.983, indicated a good correlation with the CLEIA method. Slope (a) and intercept (b) of the regression line (y＝ax + b; x for the CLEIA method, y for the FDC vc-TSH) were 0.941 and 0.077 respectively, which conﬁrmed that the measured TSH values for the FDC vc-TSH were equivalent to those for the CLEIA method (Fig. 6). Correlation test CLEIA method [ng/mL] Fig. 6 Correlation between CLEIA method and FDC vc-TSH. (2) Conﬁrmation of precision We repeatedly performed measurement on the same sample with the FDC vc-TSH and checked its precision. Table 1 shows the results of measurements performed ten times each using three test solutions with different TSH concentrations. The coefﬁcient of variation (CV), which is a criterion for variation, did not exceed 6% at any of the concentration levels. The results conﬁrmed that the reagent cartridge had sufﬁciently high reproducibility (quantitativity) for immunoassays. 3. Development of the FDC v-COR using the competitive method 3.1 Significance of the COR assay COR is among the hormones secreted by the adrenal cortex. Its blood concentration is controlled by interaction between the hypothalamus, hypophysis and adrenal cortex as follows. Inﬂuenced by adrenocorticotropic hormone (ACTH), the adrenal cortex increases the secretion of COR. The adenohypophysis secrets ACTH, stimulated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) secreted from the hypothalamus. At the same time, the secretion of those hormones is inhibited via negative feedback that occurs upon an increase of the COR concentration in the blood. In that way, the COR secretion is regulated (Fig. 7).2) Cushing s syndrome is an endocrine disorder often observed in dogs that increases the COR concentration in the blood to an abnormal level. As a basic test used for its diagnosis, the ACTH stimulation test is widely used. The syndrome is classiﬁed into two types according to the primary lesions: the hypophysis and adrenal tumor. In both cases, the COR secretion capacity has increased; therefore, the ACTH stimulation test, in which ACTH is administered, causes more COR to be secreted than usual. If the COR concentration after ACTH administration is higher than the speciﬁed value, it is diagnosed as Cushing s syndrome.3), 4) Table 1 Precision of measurements with FDC vc-TSH. (Unit : ng/mL) Corticotropin-releasing hormone Hypothalamus AVP CRH Arginine vasopressin Adenohypophysis Adrenocorticotropic hormone ACTH Cortical hormone COR Stimulation Inhibition Adrenal cortex Fig. 7 Negative feedback mechanism for adjustment of cortisol. 36 Development of Quantitative Immunoassay Reagent “FUJI DRI-CHEM IMMUNO AU Cartridge vc-TSH and v-COR” COR Immunoreaction channel (COR-BSA ﬁxed on the thin gold ﬁlm) Dissociator COR-binding globulin COR Reaction Cup 1 (Dissociator) Amount of ﬂuorescence Fluorescent particle-labeled anti-COR antibodies Solution infusion Thin gold ﬁlm Reaction Cup 2 (Fluorescent particle-labeled anti-COR antibodies) COR concentration COR-BSA Fig. 8 Principle for measuring cortisol in dog serum using FDC v-COR. 3.2 Principle of the assay with the FDC v-COR The FDC v-COR assay using the competitive method is carried out as follows (Fig. 8). (1) The serum sample is dispensed into Reaction Cup 1, which triggers a reaction between COR-binding globulins in the sample and the dissociator while dissolving and thus generates free COR [Step 1]. (2) The reaction solution in Reaction Cup 1 is dispensed into Reaction Cup 2, which triggers a reaction between antiCOR monoclonal antibodies labeled with ﬂuorescent particles (hereinafter, ﬂuorescent particle-labeled anti-COR antibodies ) and COR contained in the sample [Step 2]. At that time, the quantity of COR bound to the antibodies on the ﬂuorescent particles increases in proportion to the COR concentration of the sample. That decreases the binding sites of the antibodies. (3) The reaction solution is infused into the immunoreaction channel. COR-labeled bovine serum albumin (hereinafter, COR-BSA ) ﬁxed onto the thin gold ﬁlm formed inside the channel causes ﬂuorescent particle-labeled antiCOR antibodies to be captured onto the ﬁlm inversely proportionally to the quantity of COR bound [Step 3]. Based on the amount of ﬂuorescence obtained via the SPF method, the system performs automatic conversion to COR concentration and the assay results are thus obtained. dL when the serum sample is measured as it is.3), 4) However, in our surveys, there were some cases in which precise COR concentration measurement was requested even when the concentration exceeded 30.0 μg/dL after the ACTH stimulation test, in order to utilize the data in the precise recognition of patients conditions, the preparation of treatment plans in the future, etc. To respond to that need, we developed a reaction system that allows dilution measurement (measurement range of COR concentration: 1.0 μg/dL to 50.0 μg/dL) with which the measurement of higher-concentration areas is possible in addition to normal measurements. For high-precision dilution measurement, optimal dilution selecting and reaction condition setting are essential. We have selected saline solution that is inexpensive and easy to get in the ﬁelds of veterinary medicine, set optimal reaction conditions and thereby established reliable dilution measurement. Eliminating the necessity of the preparation of weighing instruments, complex manual dilution procedures, etc., we have realized an automatic dilution measurement function that operates by simply selecting the dilution mode on the system. : Realization of the high concentration assay with dilution measurement In the diagnosis of Cushing s syndrome with the ACTH stimulation test, 30.0 μg/dL is sufﬁcient as the upper limit of the measured COR values. Therefore, the measurement range of the FDC v-COR is set as 1.0 μg/dL to 30.0 μg/ 3.4 Clinical performance (1) Conﬁrmation of correlation To verify the effectiveness of the newly developed FDC v-COR, we conﬁrmed correlation in dog serum using CLEIA (a method employed by veterinary inspection centers) as a control method. With a correlation coefﬁcient (r) of 0.931 in non-dilution measurement and that of 0.963 in dilution measurement, the FDC v-COR indicated a good correlation with the CLEIA method in both measurements. In non-dilution measurement, slope (a) and intercept (b) of the regression line (y＝ax + b; FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 37 3.3 Main feature of the development of the reaction system Correlation test (without dilution) CLEIA method [μg/dL] Correlation test (with dilution) CLEIA method [μg/dL] Fig. 9 Correlation between CLEIA method and FDC v-COR (left: without dilution, right: with dilution). Table 2 Precision of measurements with FDC v-COR (left: without dilution, right: with dilution) < Non-dilution measurement > (Unit : μg/dL) x for the CLEIA method, y for the FDC v-COR) were 0.939 and 0.840 respectively. In dilution measurement, (a) and (b) were 0.999 and 0.285 respectively. It was thus conﬁrmed in both measurements that the measured COR values for the FDC v-COR were equivalent to those for the CLEIA method (Fig. 9). Those results indicate that the FDC v-COR enables in-clinic inspection with the same level of precision as the conventional inspection available from external organizations. (2) Conﬁrmation of precision We repeatedly performed measurement on the same sample with the FDC v-COR and checked its precision. Table 2 shows the results of measurements performed ten times, each using three test solutions for non-dilution measurement and four test solutions for dilution measurement, with different COR concentrations. The coefﬁcient of variation (CV), which is a criterion for variation, did not exceed 5% at any of the concentration levels. The results conﬁrmed that the reagent cartridge had sufﬁciently high reproducibility (quantitativity) for immunoassays. 38 < Dilution measurement > (Unit : μg/dL) 4. Conclusion We developed two new quantitative immunoassay reagents for veterinary use, FUJI DRI-CHEM IMMUNO AU Cartridge vc-TSH and FUJI DRI-CHEM IMMUNO AU Cartridge vCOR. Thus, we succeeded in providing a high-precision diagnostic method for dog hypothyroidism by applying TSH assays in combination with the T4 assay method already developed and launched last year and also established a quick and simple diagnostic method for dog Cushing s syndrome utilizing COR. Technically, we constructed a reaction system with the sandwich method in addition to the competitive method, while introducing dilution measurement into the system. In the future, based on the platform of this system, we will realize even quicker and simpler in-clinic inspection methods by improving and increasing assay items and thereby contribute to further development of animal medical care. Development of Quantitative Immunoassay Reagent “FUJI DRI-CHEM IMMUNO AU Cartridge vc-TSH and v-COR” 5. Acknowledgement We express our deep gratitude to all the members of the Imaging Materials Production Division and FUJIFILM Photo Manufacturing Co., Ltd., who made great efforts to construct the system for the manufacture of these reagent cartridges in their commercialization. References 1) Matsuno, T.; Ohara, T.; Onoda, A.; Nakamura, K.; Kimura, T.; Komatsu, A. Development of Quantitative Immunoassay Reagent FUJI DRI-CHEM IMMUNO AU Cartridge v-T4. FUJIFILM Research & Development. 2014, No.59, p. 13-18. 2) Kussingu Shoukougun Shinryo Manyuaru. Hirata, Y.; Naruse, M. eds. Shindan to Chiryo Sha, Inc., 2010, p. 9-13. 3) Canine hyperadrenocorticism (Cushing s syndrome) . Canine and Feline Endocrinology and Reproduction. Feldman, E. C.; Nelson, R. W. eds. 3rd edition, Saunders, Philadelphia, U. S. A., 2003, p. 252-357. 4) Small Animal International Medicine. Nelson, R. W.; Couto, C. G. eds. Hasegawa, A.; Tsujimoto, H. trs. 3rd edition, Interzoo, 2004, p. 811-847. Trademarks ・ FUJI DRI-CHEM and DRI-CHEM IMMUNO are registered trademarks of FUJIFILM Corporation. ・ Any other company names or system and product names referred to in this paper are generally their own trade names or registered trademarks of respective companies. FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 39 Development of a Hair Care Product Series, “ASTALIFT SCALP FOCUS” Tomoko TASHIRO*，Taichi MURAGUCHI*，Mayuko KANEHISA*，Mikinaga MORI*， Hiroyuki KITAOKA*，Tomoko THIELE*，Akihiro SUGITA**，Atsushi ORIKASA***， Takuji KOSUGI*，and Kozo NAGATA* Abstract We have launched a series of new hair care products, ASTALIFT SCALP FOCUS, which improve the elasticity and reduce the ﬁrmness of hair. Glycyrrhetinic acid, known as an active ingredient for hair growth, is insoluble both in water and in oil; therefore, this compound has been conventionally formulated with higher concentration of ethanol. However, continuous usages of high concentration of ethanol may cause dehydration and inﬂammation of the scalp. With our proprietary emulsifying technology, we have prepared nanosized (80 nm) glycyrrhetinic acid emulsion, which has high permeability into the scalp without an aid of ethanol. Furthermore, we have developed nano dispersion of human hair ceramide using our original emulsifying technology to nanosize (20 nm) human hair ceramide, which is demonstrated to permeate in human hair and to contribute to improve the ﬁrmness and the elasticity of hair. 1. Introduction FUJIFILM has developed the functional skincare products by applying our photographic expertise to the creation of beautiful skin. In September, 2007, we released the ASTALIFT skincare series based on the blending astaxanthin and three types of collagen. Subsequently, on September 24, 2014, we launched onto the market a new member of the series, ASTALIFT SCALP FOCUS, that tones up hair to healthy condition by adding to hair bounce, resilience and volume that tend to be decreased with aging (Fig. 1). In recent years, the need for anti-aging hair care products has been increasing for many women who have hair problems due to aging. The decreases of bounce, resilience and volume of hair are typical problems, which derive from age-related scalp disorders, including dehydration and inﬂammation. Therefore, it is necessary to improve the scalp condition and to apply appropriate treatment to damaged hair by infusing sufﬁcient amounts of essential active ingredients into scalp and hair. This paper reports the details of two active ingredients, blended into the ASTALIFT SCALP FOCUS: the glycyrrhetinic acid to improve the scalp condition and the human hair ceramide to enhance bounce and resilience of hair, both of which are blended as nano-emulsion. Original paper (Received December 15, 2014) * Pharmaceutical & Healthcare Research Laboratories Fig. 1 New hair care series, ASTALIFT SCALP FOCUS 2. Nano emulsion of glycyrrhetinic acid 2.1 Features of glycyrrhetinic acid Glycyrrhetinic acid is a licorice-derived, natural triterpenoid and has anti-inﬂammatory effect, and is known to inhibit the activation of hormone hair loss (5α-reductase inhibitor).1) Therefore, this ingredient has been blended into many hair growth formulas. However when blending glycyrrhetinic acid into conventional hair growth formulas, it is usually necessary to dissolve it in high-concentration, approximately 50% of aqueous ethanol solution because this reagent easily ** Research & Development Management Headquarters FUJIFILM Corporation Research & Development Management Headquarters Nakanuma, Minamiashigara, Kanagawa FUJIFILM Corporation 250-0193, Japan Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8577, Japan Analysis Technology Center Life Science Products Division *** FUJIFILM Corporation Akasaka, Minato-ku, Tokyo 107-0052, Japan 40 Development of a Hair Care Product Series, “ASTALIFT SCALP FOCUS” crystallizes and is not easily dissolved both in water and in oil. There has been concern that the continuous use of highconcentration ethanol containing hair care products would cause inﬂammation, which induce itching and/or stinging, and would worsen the scalp condition.2) To address this concern, we analyzed the effect of ethanol on the scalp cells and veriﬁed that high-concentration ethanol impairs hair papilla cells and increases the production of the cytokine IL-6, which is known to inhibit hair growth. 2.3 Permeability of glycyrrhetinic acid nano-emulsion into the epidermis We expect the nano-emulsion of glycyrrhetinic acid we developed is effectively permeate to the scalp cells. We therefore analyzed the permeability of nano-emulsion into epidermis, using 3D cultured epidermis models. The epidermis permeability of nano-emulsion of glycyrrhetinic acid was 1.7 times larger than that of the glycyrrhetinic acid dissolved in 50% ethanol the latter is usually used in ordinary hair growth formulas (Fig. 4). In general, ethanol is used as a permeation enhancer for hair care formulas. However, in this experiment where the actual concentration of glycyrrhetinic acid in the products used, the ethanol evaporated quickly just after being applied. This could condense the glycyrrhetinic acid in ethanol solution and promoted the crystallization. In contrast, the nano-suspension of glycyrrhetinic acid could keep the permeation steadily because it did not aggregate and maintained its particle size. It is thus concluded that the permeability of nano-emulsion of glycyrrhetinic acid is superior to that of ordinary glycyrrhetinic acid. FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) Nano-shell membrane Special oil 80 nanometers Glycyrrhetinic acid was dissolved in a special solvent oil and stabilized by being wrapped in a membrane (shell) that separated the constituent particles completely from water so they would not combine each other (nano-shell technology). Fig. 2 Image of nano glycyrrhetinic acid Water containing 50% ethanol containing ordinary glycyrrhetinic acid ordinary glycyrrhetinic acid Water containing nano glycyrrhetinic acid Glycyrrhetinic acid is separated from water (left). Glycyrrhetinic acid dissolved in 50% ethanol as usual (center). Nano glycyrrhetinic acid can disperse in water without ethanol (right). Fig. 3 Comparison of glycyrrhetinic acid in water (left), in 50% aqueous ethanol (middle), and water-diluted nano glycyrrhetinic acid (right) Relative horny layer permeation amount (%) 2.2 Development of nano-emulsion of glycyrrhetinic acid We therefore started to develop the methods to blend glycyrrhetinic acid into the hair care product without using highconcentration ethanol. This formula should be designed to make glycyrrhetinic acid permeate the scalp deeply through the pores. We discovered the special oil that can dissolve glycyrrhetinic acid and then develop the nano-shell technology that enables the formation of an emulsion membrane (shell) to stably emulsify the oil and this glycyrrhetinic acid. Using these technologies, we could succeed the preparation of the nano-emulsion of glycyrrhetinic acid in which a diameter of 80 nm glycyrrhetinic acid emulsions are stably dispersed in water at high density, without using ethanol (Fig. 2). Fig. 3 shows the comparison of an ordinary glycyrrhetinic acid with nano-emulsion of glycyrrhetinic acid both of which being added in water at the same concentration. It is clear that the latter can be dispersed stably and evenly in water, and is transparent. Glycyrrhetinic acid 1.7 times Ordinary glycyrrhetinic acid dissolved in 50% ethanol Nano glycyrrhetinic acid Fig. 4 Skin permeability of glycyrrhetinic acid 41 2.4 Permeability of glycyrrhetinic acid nano-emulsion to hair follicles Because there is no 3D cultured epidermis model which contain hair follicles, the evaluation of ingredient permeability through hair follicles is impossible with the 3D cultured epidermis model. We therefore considered the establishment of a new assay system that enables the localized glycyrrhetinic acid molecules to be directly visualized using excisional human scalp skin. In conventional visualization methods, the target chemical compounds are observed by tracking ﬂuorescence or pigment markers by labeling them. However, the labeling itself inﬂuences the properties of the chemical compounds, which may prevent accurate assessment. We therefore selected and introduced Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) used for the surface analysis of thin layers of functional ﬁlm, etc. TOF-SIMS can directly detect the molecular weight of chemical compounds and map them without requiring any labeling. Using this method, the locations of chemical compounds in skin can be identiﬁed. In the same way as the assessment of epidermis permeability, we applyed glycyrrhetinic acid nano-emulsion to extracted human scalp skin followed by the cryopexy. We then prepared thin-layer skin slice samples and analyzed them by TOF-SIMS. Fig. 5 shows the images of the slice to map the intensity and the location of glycyrrhetinic acid (the molecule exists in colored regions). This result indicated that the glycyrrhetinic acid could reach to scalp pores. Strength of the secondary ion Weak Strong the prevention of hair components from leaking them outside by forming the cuticle on the surface.3) The mass of CMC decreases with aging and this is considered to be one of the causes of the decrease of the bounce and the resilience of hair. To improve these hair conditions, we focused on and aimed to blend the human hair ceramide that constitutes the CMC in the hair care products. ＜Cross section＞ Cuticle Cortex Medulla Cortex Medulla Cuticle CMC ＜Enlarged view＞ Fig. 6 Structure of hair 3.2 Development of nano-dispersion of human hair ceramide The solubility of human hair ceramides is low both in water and in oil. These ceramamides easily crystallize in soluvent. Therefore, it is usually dissolved with a large amount of oil and then dispersed with solvent such as water. So the concentration of human hair ceramide is low and its diameter is large, approximately 1μm. To overcome these defects, we prepared the human hair ceramide nano-particle using the company s nano technology and succeeded in stably dispersing high-concentration human hair ceramide in water which average particle diameter is 20 nm (Fig. 7). Conventional human hair ceramide Nano human hair ceramide Fig. 5 TOF-SIMS images of glycyrrhetinic acid in a human hair follicle Fig. 7 Comparison of the transparency of nano hair ceramide and conventional hair ceramide preparation 3. Hair ceramide nano-dispersion 3.1 Hair structure and the functions of the cell membrane complex (CMC) The hair shaft consists of three layers: the medulla at the center, the cortex that surrounds the medulla and the cuticle that covers the surface (Fig. 6). The cell membrane complex (CMC) that binds those three layers together has the functions, such as, the retention of moisture inside the hair and 42 3.3 Effect of human hair ceramide nano -dispersion on hair It is known that the damage by aging, heat and UV rays degrades hair and enhances the formation of the CMC hollow. To verify the human hair ceramide nano-dispersion can repair the hollow CMC, we observed the structure of the inside of hair with a transmission electron microscope (TEM), Development of a Hair Care Product Series, ASTALIFT SCALP FOCUS After ceramide immersion Amount of human hair ceramide/1-g hair (μg) Before ceramide immersion Fig. 8 TEM images of a cross section of hair The amount of human hair ceramide doubled. Before immersion After immersion Fig. 9 Amount of ceramide in hair after treatment Before ceramide immersion After ceramide immersion Restitution rate (%) Hair bounce and resilience increased to 1.4 times Strength of the secondary ion Weak Strong Before immersion After immersion Fig. 11 Change of elasticity of hair after treatment Fig. 10 SEM and TOF-SIMS images of hair treated by nano hair ceramide and compared the structure before and after immersing the hairs in the ceramide dispersion. The results conﬁrmed that nano human hair ceramide can permeate the inside of hair via immersion and ﬁll the void of the CMC (Fig. 8). Moreover, compared with the condition before immersion, the amount of human hair ceramide in the immersed hair doubled (Fig. 9). For the conﬁrmation of the effect on the surface of hair, we observed the cuticle with a scanning electron microscope (SEM) and visualized the adsorbed ceramide with TOFSIMS. The results of SEM observation conﬁrmed that the cuticle opened because of damage was rebonded after immersion into nano human hair ceramide. The results of TOFSIMS revealed that human hair ceramide was homogeneously distributed on the surface of the hair (Fig. 10). Furthermore, the measurement of the bounce and resilience of hair with and without undergoing immersion in nano human hair ceramide indicated that immersing in it can increase those properties of hair to 1.4 times (Fig. 11). FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 4. Product evidence We selected 16 Japanese women with ages from 40 to 64 whose hair scores ranging from 2 to 4 according to the hair loss severity scores for the Japanese4) . For 24 weeks, they used the nano human hair ceramide-blended shampoo and conditioner once a day and the nano glycyrrhetinic acid-blended scalp essence twice a day (in the morning and at night after shampooing or before hair styling). Hair loss severity scoring and imaging of the crown of the head were performed by a dermatologist before use and after 12 weeks and 24 weeks of use. As a result, the average severity score decreased from 2.53 before use to 2.30 after 24 weeks of use (Fig. 12) and improvements were observed in 12 subjects out of 16. Fig. 13 shows the photo images of the crowns of two subjects as improvement examples. 43 References 1) Kiso, A. Advanced Technology of Hair Follicle Regeneration. CMC Publishing Co., Ltd., 2013, p. 213-217. 2) Endo, H.; Kobayashi, H.; Okubo, T. Contact Skin Diseases Hair loss score and Cross Reaction of Ethanol. Journal of Healthcareassociated Infection, 2009, 2 (1), p. 13-17. 3) Matsuzaki, T.; Arai, K.; Joko, K.; Hosokawa, M.; Nakamura, K. Saishin No Mouhatsu Kagaku. Fragrance Journal, Ltd., 2003, p. 308. 4) Tajima, M.; Chika Hamada, C.; Arai, T.; Miyazawa, M.; Shibata, R.; Ishino, A. Characteristic features of Japanese Before use After 12 weeks After 24 weeks women s hair with aging and with progressing hair loss. Journal of Dermatological Science. 2007, 45 (2), p. 93-103. Fig. 12 Change of hair loss score Trademarks ・ ASTALIFT, Before use SCALP FOCUS, Nano-shell, ASTALIFT/ Nano glycyrrhetinic acid and Nano human hair ceramide After 24-week continuous use are registered trademarks of FUJIFILM Corporation. ・ Any other company names or system and product names referred to in this paper are generally their own trade names or registered trademarks of respective companies. Subject 1 Subject 2 Fig. 13 Improvement examples: before (left) and after 24 weeks of continuous use (right) 5. Conclusion ASTALIFT SCALP FOCUS described in this paper is a functional hair care product that only FUJIFILM could develop by applying the company s unique technologies. We will keep improving these technologies and will engage in the development of the functional cosmetics that provide new customer values. 44 Development of a Hair Care Product Series, “ASTALIFT SCALP FOCUS” Development of Base Makeup Series “ASTALIFT LIGHTING PERFECTION” Miki KINAI*，Tomomi TATEISHI*，Kazuhiro NAKAMURA*，Terukazu YANAGI*，Ikuko OGARU*， Noriko OHIRA*，Naoko YOSHIDA**，Soichiro NAKAMURA***，Eriko IKEDA****， and Yasuko TAKEDA***** Abstract In recent years, market trends have shown increased demand for base makeup that offers a sheer-looking, ﬂawless ﬁnish and does not look overdone. Conventional powders have a technical limitation: the more sheer-looking the ﬁnish is, the less likely it is that the pores, irregular skin tone, and dark spots will be concealed; the more intensive the powder coverage, the less sheerlooking the ﬁnish is. To address this, we developed SAKURA AURA powder. With this powder, we have launched the base makeup series ASTALIFT LIGHTING PERFECTION, which offers rich, sheer-looking, and cherry blossom-like skin without losing the coverage effect. This is achieved by the soft-focus effect of the powder, which allows more red light, making the skin look beautiful, to penetrate through and reﬂect on skin, and to shine back from inside of the skin. 1. Introduction We have released the ASTALIFT cosmetics series by advancing our expertise as a photo ﬁlm manufacturer in collagen research, antioxidation technology, nano technology, photoreaction analysis and control technology. In September, 2011, we launched onto the market Light Analyzing Moisture Foundation that would make the skin look clear under a variety of light sources in daily life and have established a good reputation with its outstandingly high concealing effect on pores, irregular skin tones and pigmented spots.1) However, in recent years, market trends have shown increased demand for a sheerer, ﬁne ﬁnish without skin looking overly made-up. We therefore developed SAKURA AURA powder to resolve a technical issue of conventional powder: the more sheer-looking the powder, the less effective is the concealing of pores, irregular skin tones and pigmented spots, and vice versa. Consequently, we launched onto the market the base makeup series, ASTALIFT LIGHTING PERFECTION, Original paper (Received December 12, 2014) *Pharmaceutical & Healthcare Research Laboratories blending SAKURA AURA powder. The series realizes cherry blossom-like transparency in the skin, while maintaining perceivably high concealing performance, by utilizing the softfocus effect that allows more red light, which makes the skin ﬁner, to be transmitted and reﬂected and thereby to illuminate the skin from inside (Figs. 1 and 2).2), 3), 4) 2. Characteristics of SAKURA AURA powder - Common features between cherry blossoms and beautiful skin In the course of studying beautiful skin ideal for women, we were inspired by sakura (cherry blossoms) that most people feel beautiful as a subject of photographs. Believing that reproducing their petals fresh and clear tones and beauty in skin could lead to the expression of ﬁne skin, we analyzed their optical characteristics and sought features common between the petals and beautiful skin. Consequently, we found out that light is the key for ﬁne texture and discovered the following three properties in common: reﬂecting light homoge- **** Frontier Core-Technology Laboratories Research & Development Management Headquarters Research & Development Management Headquarters FUJIFILM Corporation FUJIFILM Corporation Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8577, Japan **Imaging Technology Center 258-8577, Japan ***** Life Science Products Division FUJIFILM Corporation Research & Development Management Headquarters Akasaka, Minato-ku, Tokyo FUJIFILM Corporation 107-0052, Japan Miyanodai, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8538, Japan ***Analysis Technology Center Research & Development Management Headquarters FUJIFILM Corporation Nakanuma, Minamiashigara, Kanagawa 250-0193, Japan FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 45 Controls red light effectively and reproduces the same optical characteristics as cherry blossoms in skin Red powder White powder SAKURA AURA powder Fig. 1 Makeup cosmetic ASTALIFT LIGHTING PERFECTION from the left, pressed powder for base makeup finish, the powder foundation long keep pact UV, and the liquid foundation moist pure liquid UV Fig. 3 SAKURA AURA powder Unstable red colorants Stabilization Fixed onto powder Bad color expression Fig. 2 Makeup eﬀect after makeup (left) and before makeup (right) neously in all directions from the surface; absorbing yellow light; and transmitting a large amount of light and reﬂecting it from beneath the surface. To reproduce those optical characteristics in skin, we developed our original powder, SAKURA AURA powder (Fig. 3). The details of the above three shared properties are described in paragraphs 2.1, 2.2 and 2.3 respectively. SAKURA AURA powder is optical powder that incorporates both red powder with a special property of absorbing yellow light that darkens the skin and white powder that reﬂects light homogeneously in all directions from the skin surface. Instead of those used in conventional ordinary foundation, we employed clear red colorants that were able to introduce red light effectively into the skin. However, they were very unstable and difﬁcult to blend into foundation as they were. To respond to that problem, we then transformed those red colorants into a stable form by ﬁxing them onto powder using our own technology (Fig. 4). 46 Transformed to stable red powder Easily aggregated Fig. 4 Modification of an unstable red colorant form stable red powder Fig. 5 Optical photomicrographs of the surface of a cherry blossom (left), beautiful skin (middle), and aged skin (right) Superﬁcial bumpy structure allowing homogeneous reflection of light in all directions from the surface We observed the superﬁcial bumpy structures of cherry blossom petals, beautiful skin and aged skin with an optical microscope and measured the intensity and angle distribution of light reﬂected from their surfaces using a goniometer. The observation results revealed that cherry blossom petals and beautiful skin had a uniform size of asperities on the surface while aged skin had various sizes of asperities (Fig. 5). The goniometer expresses the intensity of reﬂected light 2.1 Development of Base Makeup Series ASTALIFT LIGHTING PERFECTION 2.2 Absorption of yellow light that causes dullness in skin Skin naturally looks dull under yellow light with a wavelength between 570 and 600 nm used in our daily-life illumination. We measured the reﬂectance spectrum of cherry blossom petals, beautiful skin and aged skin. Fig. 9 shows the quantitative differences in their yellow light absorption rates. For cherry blossom petals and beautiful skin, the extent of decrease in the reﬂection rates of yellow light was signiﬁcant. In contrast, that for aged skin was small. In conclusion, the former two can express a darkening-free ﬁne skin tone by absorbing yellow light that causes dullness in skin and the latter looks dull because of yellow light. We then blended red powder to absorb yellow light that causes the problem into SAKURA AURA powder. White powder Reﬂection angle distribution Ideal reﬂection (perfect circle) Fig. 8 Angular distribution of the reﬂected light intensity from white powder (goniometer) Cherry blossom petal Beautiful skin Aged skin High reﬂection High absorption High reﬂection (No absorption) Reﬂection rate (%) as the size of a circle and its angle distribution as the shape of the circle (the closer to a perfect circle, the more homogeneously in all directions the light is reﬂected). The measurement results indicated that, although cherry blossom petals and beautiful skin reﬂected much light homogeneously in all directions, aged skin reﬂected a little light in only some speciﬁc directions (Fig. 6). From the aforementioned results, we found that asperities of a uniform size on the surface allowed cherry blossom petals and beautiful skin to reﬂect light evenly in all directions, while aged skin with asperities of various sizes reﬂected light in irregular directions (Fig. 7). Therefore, to ideally improve light reﬂection, we blended white powder that had homogeneously light-reﬂecting properties in all directions into SAKURA AURA powder (Fig. 8). High absorption Wavelength / nm Fig. 9 Reﬂectance spectrum and decreased reﬂection ratio of yellow light Fig. 7 Direction of the reﬂected light cherry blossom and beautiful skin (left) and aged skin (right). Photoanalysis using a one-shot visible spectrometer SD-OCT - Transmission of light and its reflection from beneath the skin surface We performed an analysis on cherry blossom petals, beautiful skin and aged skin to determine the depth from which light passing through their surfaces is reﬂected and the amount of light reﬂected. Optical coherence tomography (OCT) systems used in the medical ﬁeld are available for noninvasive biological tissue tomography. However, they take time to obtain high-precision data at a micrometer-level resolution and thus they are not suitable for the tomography of human skin that is difﬁcult to hold steady for a long time. In addition, the equipment uses a near infrared light source, which is not compatible with the optical (visible light) information of human skin. Therefore, we developed a one-shot visible spectrometer for spectraldomain (SD) OCT, using a visible light source and allowing the instant acquisition of tomographic images of the target. The optical system of the new equipment is the SD type that uses a ﬁxed-wavelength light source and spectroscope for optical coherence. The system incorporates a cylindrical lens (CL) that collects light linearly and emphasizes signal images by making the light returned from inside the skin (measurement light) interfere with reference light, which has enabled instant imaging in a mere few tens of microseconds (Fig. 10).5) FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 47 Reﬂection angle distribution Light Cherry blossom petal Beautiful skin Aged skin Cherry blossom-like skin Fig. 6 Angle distribution of reﬂected light intensity (goniometer) Cherry blossom petal Beautiful skin Aged skin 2.3 length emphasizes pores, irregular skin tones and pigmented spots, whereas red light with a long wavelength has the opposite effect. However, the mechanism was not explained yet. To discover that mechanism, we captured human skin tomographic images using the one-shot visible spectrometer SD-OCT with visible light of a variety of wavelengths applied and analyzed the relationship between the visibility of skin problems (e.g., open pores, irregular skin tones and pigmented spots) and the color of light (Fig. 12). White light source Human skin Color ﬁlters Silica glass Spectroscope Imaging lens Reference mirror C.L : Cylindrical lens Fig. 10 Optical system of one-shot visible spectrometer SD-OCT Fig. 11 Tomographic images of light reﬂected from under the skin cherry blossom (left), beautiful skin (middle), and aged skin (right). The equipment is designed so white light is passed through colored ﬁlters, allowing skin tomography with visible light having an arbitrarily selected wavelength. In addition, by simultaneously radiating red, green and blue light using the incorporated multi-wavelength simultaneous transmission ﬁlter, it can capture RGB spectroscopic tomographic images of a region all at once. Fig. 11 shows the tomographic images of a cherry blossom petal, beautiful skin and aged skin captured with the one-shot visible spectrometer SD-OCT. White areas indicate depths from which a large amount of light was returned, whereas black areas show where less light was returned. The ﬁgure indicates that aged skin reﬂects a little light from only shallow areas of the skin, while cherry blossom petals and beautiful skin reﬂect a substantial amount of light from far deeper areas. As a result, it was conﬁrmed that, like cherry blossom petals, beautiful skin looks transparent because it is bright, illuminated by much reﬂected light, and aged skin looks dull and dark with little light reﬂection. 3. Discovery of the mechanism of red light making skin look beautiful The appearance of skin, such as transparency and the visibility of open pores, irregular tones and pigmented spots, is greatly affected by the wavelength of light irradiating the skin. It is generally known that blue light with a short wave- 48 Fig. 12 Tomographic images of human skin with visible light of varying wavelength blue light (left), green light (middle), and red light (right). The detailed results are as follows. Blue light only reaches shallow areas in the horny layer and epidermal layer. The skin region that reﬂects the light is thin and the amount reﬂected is small. On the other hand, a large amount of red light reaches the upper dermic layer located deep in the skin. The skin region that reﬂects the light is wide and the amount reﬂected is large, illuminating the skin from inside. In conclusion, the depth of light transmission and the amount of light reﬂected are the factors that produce clear texture in skin. The above described skin problems can be made less conspicuous by passing a large amount of light deep into the skin and allowing much of it to reﬂect there. In that way, transparency can be given to the skin. Next, employing the slit evaluation method, we radiated red light vertically through a long slit and measured the distance that the light traveled horizontally inside the skin from that radiation position. (Figs. 13 and 14). The results revealed that foundation blended with SAKURA AURA powder allows red light to reach further and the travel distance is approximately three times longer than foundation without SAKURA AURA powder. Development of Base Makeup Series ASTALIFT LIGHTING PERFECTION Red light travel direction Blended with SAKURA AURA powder Not blended with SAKURA AURA powder Travel distance (distance until achieving the same brightness) Blended with powder Not blended with powder Distance(mm) Fig. 14 Distance travelled by red light under the skin after SAKURA AURA powder application Fig. 13 Slit evaluation method (measurement of light traveling distance inside skin) 4. Effects of makeup - Transparency compatible with concealing performance 4.1 Transparency We radiated light from the back of a silicone skin replica with imitated open pores to which foundation was applied and measured the amount of transmitted light (Fig. 15). The smaller the amount transmitted, the more transparency was lost, which made the skin look overly made-up. Conversely, the larger the amount transmitted, the clearer the skin looked. Compared with bare skin, the skin to which ordinary foundation was applied halved the transmission of light. However, the measurement results conﬁrmed that the Lighting Perfection foundation blended with SAKURA-AURA powder transmitted an amount of light nearly equal to bare skin. Fig. 15 Light transmission eﬀect in a skin replica those images (Fig. 16). We deﬁned small regions where a speciﬁed amount of luminosity decreased compared with the whole face as open pores and larger such regions as irregular skin tones. Pigmented spots were conﬁrmed visually. We calculated the percentages of the whole image area that were occupied by those skin problems both before and after the application of the foundation and compared their change rates. 4.2 Concealing performance We captured images of skin regions with problems such as open pores, irregular skin tones and pigmented spots, before and after the application of foundation blended with SAKURA AURA powder and measured the luminosity (brightness) of Pores Pigmented spots 74% reduction Before application After application Before application Fig. 16 Areas recognized as pores, PERFECTION" foundation. After application 96% reduction Before application After application Before application After application Irregular skin tones 86% reduction Before application After application Before application After application irregular skin tone, and pigmented spots greatly decreased after applying the "ASTALIFT LIGHTING FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 49 Consequently, we conﬁrmed that the areas with open pores, irregular skin tones and pigmented spots were all signiﬁcantly reduced by the application of the foundation blended with SAKURA AURA powder. 4.3 Durability The characteristic of the Long Keep Pact UV powder foundation is its durability. The foundation retains the same texture and tone as it achieved when it was applied in the morning by preventing sweat and sebum from deteriorating makeup and causing dullness in skin. It ﬁnishes the skin with a soft and resilient impression and smooth texture. Fig. 17 shows the analytical results for the clumping and deterioration of makeup 6 hours after the powder foundation was applied. Although slight changes were observed beside the nose and in the surrounding area, they didn t affect the overall impression. 4.4 Skin moisture The characteristic of the Moist Pure Liquid UV liquid foundation is its high skincare effect. The foundation contains skincare ingredients, such as astaxanthin, lycopene and three kinds of collagen, to maintain fresh skin. It ﬁnishes the skin with a fresh and radiant impression and moist texture. Fig. 18 shows the changes of skin moisture over time observed in the measurement of the skincare effect of the foundation. The results conﬁrmed that, compared with bare skin, the skin to which Moist Pure Liquid UV was applied retained moisture for a long period of time. 5. Conclusion We optically analyzed cherry blossom petals that everybody feels beautiful as a subject of photographs using the one-shot visible spectrometer SD-OCT. We then developed the optical powder, SAKURA AURA powder, by reproducing the optical properties of cherry blossom petals in it and blended it into foundation. The foundation achieves high transparency in skin, while exhibiting excellent concealing performance. Speciﬁcally, the foundation has light transmittance of the same level as bare skin together with a high makeup effect as a base makeup item to conceal common skin troubles, such as open pores, irregular skin tones and pigmented spots, and to realize beautiful skin ideal for women. In the future, we will keep utilizing our expertise accumulated in photography for the realization of ideal beautiful skin and, via product development activities based on the novel perspective and scientiﬁc attitude characteristic to FUJIFILM, we are going to contribute to the improvement of women s beauty. References 1) Nakamura, K; et al. Development of Concept behind ASTA LI FT Light A nalyzing Moist u re Fou ndation. FUJIFILM Research & Development. 2012, no. 57, p. 11-14. 2) FUJIFILM News Releases. Jun. 19, 2014. http://www.fujiﬁlm.co.jp/corporate/news/articleffnr_0884.html. 3) FUJIFILM News Releases. Jun. 23, 2014. http://www.fujiﬁlm.co.jp/corporate/news/articleffnr_0885.html. 4) FUJIFILM News Releases. Jun. 30, 2014. http://www.fujiﬁlm.co.jp/corporate/news/articleffnr_0888.html. 5) Yoshida, N.; Tani, T.; Ishibashi, H.; Naya, M. Optical analysis of dullness and translucence of the skin using optical coherence tomography (OCT) and polarized light imaging. Fragrance Journal. 2013, 41 (3), p. 29-35. Trademarks Fig. 17 Makeup endurance of the powder foundation long keep pact UV measured 6 hours after application ・ ASTALIFT, ASTALIFT LIGHTING PERFECTION and SAKURA AURA referred to in this paper are registered trademarks of FUJIFILM Corporation. ・ Any other company names or system and product names referred to in this paper are generally their own trade names or registered trademarks of respective companies. Fig. 18 Moisturizing eﬀect of the liquid foundation moist pure liquid UV ; changes in skin moisture over time 50 Development of Base Makeup Series ASTALIFT LIGHTING PERFECTION High Functionality of UV Inkjet Inks Produced by Combining an N-vinyl Compound Tsutomu UMEBAYASHI*，Toshiyuki MAKUTA*，Mamoru TANABE**，Tadao SHIBAMOTO**， and Takahiro HAMAMOTO** Abstract Demand continues to increase for digitized signs such as wide-format indoor and outdoor advertisements, posters, and retail store POPs; such digitized products may be fabricated by vacuum forming or heat forming. To meet the growing demand, the Fuji Film group has conducted research and development projects for highly functional ultraviolet (UV) ink-jet inks. Since 2010, the Fuji Film group has launched a high-sensitivity ink and a vacuum-forming ink. High sensitivity and compatibilty with vacuum forming were accomplished by combining an N-vinyl compound (NVC) with an acrylate compound, which has been widely used in UV ink-jet inks. The purpose of this report is to describe how the NVC contributes to the increased sensitivity and to suitability as a vacuum-forming ink. First, we discuss how the NVC improves the sensitivity of a UV ink-jet ink, then we explain the role the NVC plays in a vacuum-forming ink. 1. Introduction Since the beginning of the trend toward digital printing around 2000, the use of wide format inkjet printers with UV inkjet ink has expanded in the signage printing market involving wide-format, indoor and outdoor advertisements, posters, retail store POPS, etc. In recent years, the market has been experiencing yet another trend: the subdivision of customer needs such as improved productivity, a wider variety of media types, higher image quality and energy saving.1) Also in the vacuum-formed and heat-formed signage domain that is overdue for digitalization, demand for streamlined processes and graphical design has been increasing and requests are often heard for improvements in the compatibility of UV inkjet ink for vacuum forming. To respond to those requests, the FUJIFILM group has carried out research and development of higher-functionality UV inkjet ink and, from 2010, the group has released products, such as high-sensitivity ink and vacuum-forming ink, for that domain. The high sensitivity of those inks and their suitability for vacuum forming have been realized by introducing N-vinyl compounds (Fig. 1) in combination with the acrylate compounds (Fig. 2) used widely in conventional UV inkjet ink. The purpose of this paper is to provide an understanding of Fig. 1 Example of an N-vinyl compound for UV IJ inks. Original paper (Received January 14, 2015) * Advanced Marking Research Laboratories the functions of N-vinyl compounds in high-sensitivity ink and vacuum-forming ink. First, we veriﬁed the mechanism of high sensitivity of UV inkjet ink using N-vinyl compounds. We then studied the functions of N-vinyl compounds in vacuum-forming ink. 2. Functions of N-vinyl compounds in high-sensitivity ink Including the ink (product code: LL) for the LED-incorporated printer released in 2012, Acuity 1600 LED, our high-sensitivity ink products utilize a characteristic of Nvinyl compounds (NVCs) that mixing them with acrylate compounds at a speciﬁed ratio achieves high sensitivity.2) Fig. 3 shows an example of that characteristic. By maintaining NVCs between approximately 20 and 50% of the total polymerizable compounds in ink, the ink ﬁlm can be made tack-free (no surface sticky) with a small UV radiation count. That is, maintaining the NVC proportion within that range can increase curing sensitivity. Fig. 2 Example of an acrylate compound for UV IJ inks. ** Analysis Technology Center Research & Development Management Headquarters Research & Development Management Headquarters FUJIFILM Corporation Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa Nakanuma, Minamiashigara, Kanagawa 258-8577, Japan 250-0193, Japan FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 51 Relative sensitivity* NVC proportion of the total polymerizable compounds NVC concentration in ink (wt%) Concentration of total acrylate compounds in ink (wt%) NVC proportion of the total polymerizable compounds X % Fig. 3 *Relative sensitivity : Exposure count at which the tack-free property is achieved Relation between curing sensitivity and the NVC ratio in total polymerizable compounds in inks. Ink using NVCs mixed with acrylate compounds has higher sensitivity than that using one of those two compounds alone. That characteristic mechanism is veriﬁed separately for each elementary process of (i) initiation reaction, (ii) propagation reaction and (iii) termination reaction as follows. are not highly active in polymerization reaction with NVCs. In contrast, mixing acrylate compounds accelerated double bond disappearance (Fig. 4-2). As a result, it can be considered that radicals on NVCs are sufﬁciently active in polymerization reaction with acrylate compounds. On the other hand, according to analysis using nuclear magnetic resonance (NMR) spectroscopy of the polymers generated in ink whose NVC and acrylate compound mixing ratio was 30:70, the component ratio of the N-vinyl monomers and acrylate monomers in the generated polymers was approximately 30:70. It is thus indicated that radicals on acrylate compounds can be sufﬁciently active in polymerization reaction with NVCs. (iii) Termination reaction Termination reaction in radical polymerization can be exInactivation (Polymerization inhibition by oxygen) (i) Initiation reaction Termination of rebonding Photopolymerization initiator UV rays Initiator radical Acrylate monomer NVC monomer Acrylate monomer radical NVC monomer radical Scheme 1 Radical generation and initiation reaction Table 1 shows the initiation reaction rates of initiator radicals (P radicals generated from acylphosphine oxide) with NVCs and with acrylate compounds measured with the nanotransient absorption measurement method. NVCs had an approximately one-digit larger value for the reaction rate constant than acrylate compounds. Table 1 Initiation reaction rates for the P radical and each monomer; reaction rates estimated by nanotransient absorption measurements. (ii) Propagation reaction Repetition Acrylate-NVC polymer Scheme 2 Propagation reaction According to the results obtained via real-time IR measurement, NVCs did not promote double bond disappearance by themselves (Fig. 4-1), which indicates that radicals on NVCs 52 Scheme 3 Termination reaction plained by the generation of low-activity peroxyl radicals mainly via the reaction between radicals and oxygen. It has not been conﬁrmed yet in the past study whether NVCs have signiﬁcant differences in reactivity with oxygen, compared with acrylate compounds. From the analytical results obtained thus far, the mechanism that improves sensitivity of UV inkjet ink with NVCs is inferred as follows. In general, acrylate-base radical UV inkjet ink has low viscosity compared with analog UV ink, such as screen ink, allowing oxygen from the air to easily diffuse into the ink. It is said that the ink is thus strongly affected by oxygen s inhibiting of polymerization.3) Therefore, for the improvement of the sensitivity of UV inkjet ink, it is considered to be an effective method to enhance the initiation reaction (i) and the propagation reaction (ii) relatively to the termination reaction (iii) of polymerization inhibition by oxygen. Here, two main observations can be made. Firstly, the high reactivity of NVCs with initiator radicals contributes to the enhancement of the initiation reaction of ink that uses NVCs. However, if ink monomers are composed of only NVCs, the propagation reaction will not progress and the curing sensitivity becomes low because reactivity between NVC radicals and NVCs is low. Secondly, and in contrast, the reactivity of NVC radicals with acrylate compounds is sufﬁciently high. Mixing the two compounds can thus prevent the slowdown of the propagation reaction. It can be concluded from the above observations that ink using NVCs mixed with acrylate compounds at a speciﬁed ratio has higher sensitivity than that using one of those two compounds alone. Functionality of UV Inkjet Inks Produced by Combining an N-vinyl Compound Fig. 4-1 Results from IR measurements for a polymerization system in the presence of an acrylate compound and in the presence of an N-vinyl compound. The measurements determined, from the start of irradiation (t = 0 s), the change in absorption (λ = 1626 cm-1 ) caused by double bonds. Fig. 4-2 Same as in Fig. 4-1 but in the presence of both an acrylate compound and an N-vinyl compound. Fig. 5 Examples of a vacuum-forming product digitally formed by an UV inkjet ink (KV). These examples show trial productions of the dashboard of a car (left) and of a three-dimensional signboard used at stores and other commercial facilities. Fig. 6 Example of a crack. A linear crack formed mainly on a part of the edge of a three-dimensional object. When the sample is formed normally, it becomes uniformly white. Fig. 7 Example of blocking. After printing, the print side and the backside were placed on top of each other. After storing for 24 hours, blocking occurred in which an ink film (black) became attached to the backside (white matrix). The vacuum-forming ink (product code: KV) launched onto the market in spring, 2014 has enabled digital-printed decoration to be applied to vacuum-formed products and has brought advantages to many users in the streamlining of manufacturing and development processes and the diversiﬁcation of design (see Fig. 5 for product examples). The ink s compatibility with vacuum forming is achieved by a physical property of ﬁlm: cured ﬁlm is rigid at room temperature but it becomes ﬂexible enough at high temperatures between 80 and 200℃ to be stretched up to 1000%. That characteristic physical property is yet another function given by using NVCs. Vacuum forming using UV inkjet ink designed for conventional wide format graphics generates cracks in the decoration layer (ink ﬁlm) (Fig. 6). The cause of the cracking can be explained by insufﬁcient stretchability during forming (at high temperatures) due to the high crosslink density of crosslinked polymers composing the ink ﬁlm. The veriﬁcation results obtained thus far indicate that, to give heat stretchability of 1000% or higher (PET substrates/200℃ heating), ink with almost no crosslinking components (polyfunctional monomers) is required. That is, the polymerization dilution used in the ink must be composed of only monofunctional monomers. Vacuum-forming inks provided by other companies consist of only monofunctional monomers. They have achieved an FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 53 3. Functions of N-vinyl compounds in vacuumforming ink excellent stretchability at high temperatures by reducing the crosslink density. However, there is a risk of blocking by doing so. Blocking is a problem in which the ink ﬁlm adheres to substrates when printed matter is stored in piles at room temperature (around 25℃) (Fig. 7). It is necessary for users to exercise proper caution when storing printed matter. KV ink has succeeded in the prevention of both cracking and blocking by selecting a formulation pattern of two items: no crosslinking components and NVCs. Its cracking and blocking prevention mechanisms are explained below using viscoelasticity measurement results for (1) ink without crosslinking components (including NVCs), (2) ink with crosslinking components and (3) ink without crosslinking components (not including NVCs) and the conceptual images of their polymerized ﬁlms (Fig. 8). sively soft ﬁlm causes blocking when printed matter is stored in piles. Ink without crosslinking components but including NVCs (1) is equivalent to KV ink. The ink ﬁlm is composed of linear polymers without crosslinking components. Thus, the ﬁlm has a low elasticity at forming temperatures (greater than 80℃), allowing sufﬁcient heat softening. In addition, the linear polymers are modiﬁed by NVCs. NVCs have a rigid ringshaped framework and the cured ﬁlm has a high elasticity as well as a Tg (glass-transition temperature) higher than room temperature. For example, the Tg of NVPs is 80℃ and that of NVCs is 90℃. The modiﬁcation of linear polymers by that rigid framework increases elasticity, achieving a ﬁlm rigid enough to prevent blocking at room temperature. 4. Conclusion Ink with crosslinking components (2) has an excessively high elasticity at forming temperatures (greater than 80℃). Therefore, cured ink ﬁlm cannot adapt quickly enough to the deformation of substrates softened by heating and that causes cracking. Ink without crosslinking components (not including NVCs) (3) has a sufﬁciently low elasticity at high temperatures. The ﬁlm softens to the same extent as substrates by heating. Thus, cracking does not occur during forming. However, elasticity at room temperature is too low, which means that exces- We veriﬁed the functions of N-vinyl compounds (NVCs) utilized in the high-sensitivity ink and vacuum-forming ink we have developed since 2010. The results conﬁrmed that the mechanism to improve sensitivity can be explained by two characteristics: the reactivity between NVCs and initiator radicals is extremely high; and the reactivity of NVC radicals with NVCs is low but that with acrylate compounds is sufﬁciently high. With regard to NVCs utilized in vacuumforming ink, it has become clear that they have functions to improve the elasticity of linear polymers at room temperature without increasing the crosslink density. Elasticity of cured ink film References Elasticity Ink with crosslinking components Ink without crosslinking components (including NVCs) Ink without crosslinking components (not including NVCs) 1) Kasai, S. Current Situation and Future Trends of UV Inkjet Systems. Journal of Printing Science and Technology. 2008, 45 (6), p. 602-608. 2) Sato, T. Wide Format UV Inkjet Printers. Journal of Printing Science and Technology. 2013, 50 (5), p. 407-412. 3) Caiger, Nigel; Herlihy, Shaun. Oxygen Inhibition Effects Temperature Ink with crosslinking components Ink without crosslinking components (non-hybrid type) in UV-Curing Inkjet Inks . IS&T s NIP15: International Ink without crosslinking components (hybrid type) Conference on Digital Printing Technologies. Orlando, 199910-17/22, IS&T. 1999, p.116-119. Trademarks ・ Company names or system and product names referred to in Crosslink Crosslinked polymer Heat stretchability × Blocking　　　　 ○ this paper are generally their own trade names or registered Linear polymer Heat stretchability ○ Blocking　　　　 × Heat stretchability ○ Blocking　　　　 ○ trademarks of respective companies. Fig. 8 Results from viscoelasticity measurements and schematic diagrams of polymerized films for (1) ink without the crosslinking component (but including NVC), (2) ink containing a crosslinking component, and (3) ink without a crosslinking component (but not including NVC). 54 Functionality of UV Inkjet Inks Produced by Combining an N-vinyl Compound Development of a Long-life Processing System for Newspaper CTP Plates (LL-6) Toshihiro WATANEBE* and Tomoki OCHIMIZU* Abstract We have developed the ECONEX NEWS LL-6KIT for the newspaper printing industry. The LL-6KIT reduces the amount of waste ﬂuid by improving the processing performance of thermal negative CTP processing systems. By installing the LL-6KIT in an existing machine, the processing performance of a conventional newspaper CTP system can be increased by a factor of six. We have decreased the number of waste ﬂuids in two ways. The ﬁrst is by designing a new circulation that redistributes precipitates in the developer tank; an additive is introduced to control accumulation of aluminum when washing in clear water. The second is a technology that involves distillation to concentrate waste ﬂuids of both developer and washing water. Additionally, some machine parts have been newly designed. Consequently, it is now possible to extend liquid exchange every six months, and the amount of exhaust CO2 is reduced because of the signiﬁcant reduction in the amount of waste ﬂuids. 1. Introduction CTP plate supports to make new ones (awarded the 2012 In recent years, the printing industry has been making efforts to reduce its load on the environment. Among those efforts is the encouragement for companies to introduce ecological printing systems, such as the Green Printing certiﬁcation scheme of the Japan Federation of Printing Industries. FUJIFILM started to support environmentally friendly products for the printing industry in the early stage of that movement and has widely engaged in environment-conscious design and the development of manufacturing technology through product life cycles of offset printing plates. The following are green products we developed particularly for the newspaper printing market. Encouragement Prize for Resource-recycling Technologies and Environment-conscious systems for the FUJIFILM graphic market (newspapers) Systems by the Japan Environmental Management Association for Industry) ・LP-940 NEWS automatic processor for 4 × 1 printers that saves resources by downsizing (2012) As a new member of the above lineup, we have developed the ECONEX NEWS LL-6KIT, a kit that extends the lifespan of automatic processors for newspaper printing, and gives eco-friendliness to the thermal negative newspaper CTP system, HN-NV, by improving processing performance (Fig. 1). 2. Development concept In the ﬁeld of Japanese newspaper printing, the following have been signiﬁcant issues: the improvement of print surface ・Energy-saving and space-saving, ovenless thermal negative CTP system, HN-N (2004)1) ・HN-N II computer-to-plate (CTP) system that enables resource saving and waste reduction without requiring prewashing and interleaf paper insertion (2007)2) ・XR-2000/5000 that reduces liquid waste by concentrating waste developers among industrial waste (awarded the 2009 Encouragement Prize for Technology by Nihon Shinbun Kyokai)3) ・HN-NV CTP plate that intends to reduce lost printing sheets to the minimum by improving printing performance (2009) ・PLATE to PLATE System that recycles aluminum used in Fig. 1 ECONEX NEWS SYSTEM & LL-6KIT Original paper (Received December 5, 2014) * Research & Development Center Production, Research & Development Headquarters FUJIFILM Global Graphic Systems Co.,Ltd. Kawashiri, Yoshida-cho, Haibara-gun, Shizuoka 421-0396, Japan FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) 55 quality and resource saving (reduction of materials, workload, energy, the amount of CO2 emission and water used, etc.) Normally, we recommend replacing mother solution for newspaper CTP plates every month or 3,000 m2 (whole tank simultaneous replacement) when they are used in combination with the LP-1310 NEWS II automatic processor. However, in the case of newspaper companies that own several printing plate manufacture lines, solution replacement should take place very frequently (almost every week if they have four lines) and that has been a great burden on-site. If it becomes possible to achieve the same level of processing performance as the ECONEX II environmentally friendly CTP system for commercial printing (solution replacement every six months or 30,000 plates), the reduction of environmental load, liquid waste disposal cost and chemical cost can be expected, in addition to the reduction of workload of solution replacement, by reducing the mother solution waste produced when it is replaced and primary washing waste. If that is possible by a simple upgrade without changing the current plates and processing solution or replacing the existing auto processor, customers can introduce the alteration at ease without considering capital investment or the disposal of waste deriving from the upgrade. Moreover, because the workload of the staff members involved in the solution replacement process is reduced, they have more time to engage in other work and that also contributes to the increase of overall work performance. We therefore started to develop the ECONEX NEWS LL6KIT, aiming to realize a long life of six months (or 18,000 m2) not only in commercial CTP but also in newspaper CTP processing systems and thereby contribute to eco-friendliness and resource saving in this domain. 3. Characteristics and issues of newspaper CTP processing systems The current newspaper processing system generates blue precipitation (Fig. 3) in the developer tank of the automatic processor (Fig. 2) and, according to the amount of accumulated precipitation, its lifespan is set to one month (or 3,000 m2). The newspaper CTP plate has a radical polymerization- type photosensitive layer consisting of infrared-photosensitive sensitizing dyes, radical generators, polymerizable monomers, alkali-soluble binders and colorants. Excited by IR laser exposure, the sensitizing dyes transfer electrons to the radical generators. That generates radicals, causing a radical chain reaction between polymerizable monomers. Images are thus developed. Colorants, which lack polymerization inhibition properties, are used to enable the printing plates to be effectively inspected. However, the colorants are not soluble in alkaline developers and will precipitate in them. To clarify the issue, we carried out a long-term processing test with the current system. According to the results, precipitation occurred most easily at a position where the circulation ﬂow inside the developer tank becomes weak and where the printing plate transport line comes close to the bottom of the tank. The results also revealed that in a two-month (6,000 m2) operation, precipitation nearly reached the height of the transport line. At that point of time, no degradation due to precipitation was observed in appearance or printing performance in our internal assessment. However, there was still concern about adverse effects on the processing plate as well as washing performance degradation by the accumulation of dirt inside the automatic processor if precipitation became more severe. In the meantime, we also conducted a market survey. The results revealed that, in addition to precipitation accumulated inside the developer tank, clogging occurred sporadically in the piping for the rinsing section of an automatic processor that had been used for a few years. Based on the above ﬁndings, we set the following three items to be our goals for the development of technology to extend the lifespan of the current processing system: homogenous dispersion of the photosensitive layer inside the developer tank; inhibition of precipitation inside the washing tank circulation system (as well as inside the drain pipes); and suppression of the drying and adhesion of fatigued developers inside the automatic processors. Newspaper thermal CTP processor World’s lowest level of developer reﬁlling frequency and liquid waste generation Developing Rinsing Fin Drying Fig. 2 The plate processor & developing process for newspaper CTP plate 56 Fig. 3 Precipitation in a present developer tank Development of a Long-life Processing System for Newspaper CTP Plates (LL-6) 4.1 Technology for the homogenous dispersion of the photosensitive layer inside the developer tank In the past, we carried out research on the removal of the precipitation of non-soluble colorants. However, we were unable to make the expected improvements with ﬁltrationmethod or precipitation-method removers and abandoned the project. This time, we invented a simple removal mechanism that inhibited precipitation by enhancing the dispersion properties of the colorants inside the developer tank and discharged any precipitation together with the overﬂow liquid waste. The design concept is illustrated in Fig. 4. Thus far, we have increased the circulation ﬂow at the Current system LL-6 system Fig. 4 Model chart of precipitation decentralization New : Developer tank speciﬁcations after the improvement of its mixing performance Conventional developer tank speciﬁcations Full-width spray Half-width spray Sprays at the heater base Cover above the heater Fig. 5 Re-blueprint on circulation style in developer tank Height of precipitation (index) Height of precipitation accumulated at the bottom of the developer tank Target level Conventional system ECONEX NEWS system Amount processed (m2) Fig. 6 Amount of precipitation in developer tank FUJIFILM RESEARCH & DEVELOPMENT (No.60-2015) back of the developer tank where the mixing performance is weak, made the overall mixing performance of the tank homogenous and increased the capacity of the circulation pump to slow the precipitation speed. Moreover, we have invented a precipitation guidance circulation channel allowing the replacement of solution most efﬁciently and redesigned the shape and positions of the submerged sprays (Fig. 5). Fig. 6 shows changes in the height of precipitation at the center of the developer tank where precipitation accumulates most easily. 4.2 Technology for the inhibition of aluminum hydroxide precipitation inside the rinsing tank circulation system (as well as inside the drain pipes) Having received expressions of concern from several companies about the clogging of the rinsing tank circulation pipes and liquid waste piping, we carried out an analysis and found out that the precipitate was aluminum hydroxide. The solution replacement cycle needed to be extended to achieve a longer-life processing system. Therefore, we studied a method for the prevention of deposits inside the rinsing pipes based on the assumption of its occurrence mechanism: aluminum elutes from the printing plate into the alkaline developer; it solidiﬁes in the developer because it is a highly alkaline solution; however, aluminum that is brought out from the developer into the rinsing section via the printing plate surface precipitates as aluminum hydroxide due to the decrease of pH and clogs the pipe there. To inhibit precipitation even when the pH is decreased in rinsing water, we produced a rinsing water additive with a chelating ability, HN-T, and decided to add it quantitatively to the rinsing tank. We investigated changes in the concentration of aluminum in rinsing water during the running of the system, identiﬁed the minimum amount of chelating ability required, and determined the amount of HN-T to be added. Fig. 7 shows the simulation results for the chelating abilities of the conventional system and the ECONEX NEWS system. Correlation between the amount processed and the concentration of the rinsing water additive HN-T Chelating ability 4. Technology employed in the ECONEX NEWS LL-6KIT ECONEX NEWS system Minimum amount required Conventional system Amount processed(m2) Fig. 7 Change in chelating capacity by HN-T 57 4.3 Suppression of the drying and adhesion of fatigued developers inside the automatic processor In many cases, under the current solution replacement frequency (every month), intermediate maintenance is seldom performed. Therefore, our goal was the realization of a maintenance-free, six-month (or 18,000 m2) lifespan. To achieve that, we introduced a structure for the suppression of drying inside the automatic processor, such as an automatic washing function for ﬁnishing rollers and driving gear drying prevention function. In addition, we incorporated a drying suppression mechanism into components for the parts where the fatigued developer containing photosensitive layer constituents repeatedly adheres and dries, and subsequently redesigned it. We thus enabled six-month, washingfree operation including a three-day continuous stop period. 5. Conclusion The purpose of the development of the ECONEX NEWS LL-6KIT for longer life of processing systems was to give environmental friendliness to the existing automatic processor LP-1310 NEWS II. We have established the ECONEX NEWS System by using the kit in combination with the XR liquid waste reducer and XR-R recycled water reuse system (Fig. 8). We veriﬁed the amount of liquid waste reduced by this system, comparatively, using CO2 emission (LCA values). The results conﬁrmed that, as intended, CO2 emission can be reduced substantially in the processing agent disposal process. The details are shown in Fig. 9. 6. Afterword The ECONEX NEWS LL-6KIT described in this paper is an innovative processing system that dramatically improves the environmental performance of newspaper CTP plates. By simply attaching it to the existing automatic processor LP-1310 NEWS II, it reduces CO2 emission during the disposal of processing agents to approximately one-fourth while maintaining the same quality as before. We hope that this kit will be introduced into the automatic processors of many newspaper companies and contribute greatly to resource saving in the Japanese newspaper printing industry (reduction of materials, workload, energy, amount of CO2 emission and water used, etc.) References Fig. 8 Image of ECONEX NEWS system 1) Goto, T.; Kunita, K.; Yanaka, H. Development of Thermal Negative CTP System HN-N for Newspaper Printing. FUJIFILM Research & Development. 2005, no. 50. pp. 55-59. CO2 emission of the newspaper CTP “ECONEX NEWS” Conventional system (Without XR) CTP HN-N II for Newspaper Printing. FUJIFILM Research & Development. 2009, no. 54. pp. 6-9. ECONEX NEWS (With XR) LCA value 2) Arimura, K.; Endo, A. Development of Thermal Negative 3) Watanabe, T.; Ochimizu, T.; Goi, H.; Yamamoto, H. Preprints of the 130th Conference of the Japanese Society of Printing D is po a os sp Di f lo es oc pr ng li yc c Re m ip qu e of en l s ial er at tm ta g sin ts en ag To en t pm ui sa l oc pr of po es g ra e Op g tin g sin ts en ag eq w er n io at rt tin po pe ra an s ia Tr er at m en t pm ui Eq an M e ur ct a uf of eq t en m p ui O ls Science and Technology. 2013, A-02. Trademarks ・ PLATE to PLATE and ECONEX referred to in this paper are registered trademarks of FUJIFILM Corporation. ・ Any other company names or system and product names Fig. 9 Carbon-dioxide emissions of ECONEX NEWS system referred to in this paper are generally their own trade names or registered trademarks of respective companies. 58 Development of a Long-life Processing System for Newspaper CTP Plates (LL-6) Editorial Note Innovation is the current buzzword. We hear it frequently on-site. The word is used in various contexts, but it always conveys adding new value (and subsequently, culture) to the lifestyles and behaviors of people, organizations, and society by creating novel technology and systems. Apple s iPod and iPhone are good examples. Regardless of scale, with the right idea, innovations are possible anywhere. The key to success is whether you understand an innovation s value for your customers; however, that understanding is not possible if you close yourself off from the outside world. Within an R&D environment, new inventions are constantly being examined. To elevate those inventions to innovations, I believe it is very important to explore the vast world with curiosity, maintain an enterprising spirit, and take dynamic action. This journal is issued every year to introduce our R&D achievements. It describes our new products and the novel technologies developed on-site. Do not assume that the papers do not apply to your domain. Keep an open mind. Read them with curiosity. Reading the journal could spark inspiration and help you create innovative products. Toshiaki Aoai Editor in Chief Editional Board Editor in Chief Toshiaki Aoai Editors Masashi Aoki Akira Kurisu Masatoshi Nakanishi Keitaro Aoshima Akio Kobayashi Hiroshi Nagate Yoshiyasu Inami Hiroyuki Suzuki Satoshi Matsubaguchi Atsushi Uejima Hiroyuki Seki Takeshi Misawa Takayuki Kasahara Hiroo Takizawa Hiroyasu Yamamoto Editorial Staff Atsushi Matsunaga Jun Kubota Norie Futamura Motoshi Otsubo Publisher Naoto Yanagihara

Fujifilm Research Development No.060 (pdf: 9.2mb)

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